Bat Coronavirus Research Articles

Bushmeat and zoonoses threats warrant need for national zoonoses combat inter-disciplinary research partnership, evolving citizen science and policy ban of trade and consumption

<p class="Noindentpara">“We must find them before they find us” said Dr.Shi, Bat Virologist”. Indian bat species diversity stands 127 ssp and China 147 bat ssp. Indian publications online (2000-2020), searching “bat”, “Chiroptera”, “India”, retrieved results viz., 191 (Elsevier); 27 (Scopus) and 0 (Wiley). For China, 594 publications exist (2000-2017)2; Himalayan cave bat biodiversity is not systematized, average annual deforestation rate, from 2000 to 2014 being 0.5% (Bhutan, Nepal) but 1.3% in India, China. “Dilution effect”, so-called “negative diversity–disease”, says ‘biodiversity losses promote disease transmission’. Protecting natural areas from human incursion reduces zoonotic disease spillover. Emergence of bat coronavirus represents recent viral explosion reaction to declining biodiversity. Meta-analysis of 143 hunting studies from India showed 114 mammal species but bat-hunting data absent.</p>

COVID-19. SARS-Cov-2 pandemic, transmission pathways, distribution features, and individual susceptibility

In December 2019, an outbreak of pneumonia of unknown etiology was registered in Wuhan, Hubei province of the people's Republic of China. The virus was soon isolated and its genome sequenced. It is called the severe acute respiratory syndrome coronavirus‑2 (SARS-Cov-2, English SARS-Cov-2), and the disease caused by it is coronavirus infection – 19 (English COVID-19). Who recognized the COVID-19 outbreak as a pandemic on March 11. The entire world is currently affected by the pandemic. The first focus of coronavirus infection in Russia was detected on February 27, brought from Europe. The infection reached the most remote corners of Siberia by mid-April. The aim of this study is to analyze the characteristics of SARS-Cov-2, its pathways into the body and individual susceptibility to the virus. Methods and materials. The review of scientific articles on the research topic was based on the analysis of scientific articles on COVID-19. Articles were searched in the Web of Sciences, Scopus, PubMed, and eLIBRARY databases, as well as by article links. Results. The SARS-Cov-2 virus is a single-stranded positive-chain RNA virus from the Coronavirus family (Coronaviridae). According to most researchers, the SARS-Cov-2 virus evolved from bat coronaviruses, with the approximate time of divergence from the nearest bat virus species RaTG13 occurring in 1963. It uses ACE-2 receptors, which are widely present throughout the body, to enter host cells. High virus contagiousness is provided by the acquisition of an additional furin site for cleavage of the spike protein in the form of the amino acid sequence Arg-Arg-Ala-Arg (682RRAR685). This site of the S1 domain of the spike protein can be cleaved by: transmembrane serine protease 2 (TMPRSS2), furin, but also many cellular and extracellular proteases, as well as plasmin(ogen) s. Many ways of cleavage of the spike protein significantly increase the ability of the virus to enter the cell and its contagiousness. The main routes of transmission of SARS-Cov-2 are respiratory drops and close contact. The main entrance gate of the virus is the respiratory tract, may be conjunctiva, likely fecal-oral pathway. The article discusses the skin as an entrance gate. Some skin manifestations of the disease can be caused by this way. The incubation period of COVID-19 lasts on average 5-6 days, while the live infectious virus begins to be released 2-3 days before the first symptoms appear and stops on the 8th day after the symptoms appear, but only in severe patients the virus release can last up to 15 days. Asymptomatic patients may account for 40% of cases. Features of individual susceptibility to COVID-19 and the severity of clinical manifestations may be caused by: 1) the property of allelic variants of the virus and their virulence; 2) the infectious dose of the virus; 3) the use of protective equipment; 4) individual characteristics of the human body; 5) pathogenic mechanisms of infection development. The hypothesis of the protective role of the mumps vaccine explains the phenomenon of extremely low morbidity, asymptomatic or mild infection in children more convincingly. Mass vaccination against mumps in our country began in 1981 (39 years ago), which is probably why children and people under 40 rarely get a severe form of infection in our country. Conclusion. SARS-Cov-2 has pandemic potential and is estimated to be more severe than pandemic influenza viruses. Active isolation of the virus before the onset of symptoms, including by asymptomatic patients (including children), causes the rapid spread of infection and reduces the effectiveness of anti-epidemic measures. The presence of a significant segment of the population with cross-immunity to SARS-Cov-2, including and as a result of vaccination, it is the most likely cause of a high percentage of asymptomatic and mild forms of the disease among children and young people. Effective protection against coronavirus infection in 2019 can only be achieved by taking comprehensive measures to prevent the virus from entering the body through the respiratory tract, per os, conjunctiva and skin, although the latter pathway is not taken into account anywhere in the world. It should be noted that COVID-19 cannot be classified as a particularly dangerous infection, but its high contagiousness, the likelihood of multiple entry gates of the virus into the human body, multi-organ lesions and a high mortality rate of risk groups make it a special infection that requires significant efforts of humanity to eliminate it.

COVID-19-neutralizing antibodies predict disease severity and survival

Coronavirus disease 2019 (COVID-19) exhibits variable symptom severity ranging from asymptomatic to life-threatening, yet the relationship between severity and the humoral immune response is poorly understood. We examined antibody responses in 113 COVID-19 patients and found that severe cases resulting in intubation or death exhibited increased inflammatory markers, lymphopenia, pro-inflammatory cytokines, and high anti-receptor binding domain (RBD) antibody levels. Although anti-RBD immunoglobulin G (IgG) levels generally correlated with neutralization titer, quantitation of neutralization potency revealed that high potency was a predictor of survival. In addition to neutralization of wild-type SARS-CoV-2, patient sera were also able to neutralize the recently emerged SARS-CoV-2 mutant D614G, suggesting cross-protection from reinfection by either strain. However, SARS-CoV-2 sera generally lacked cross-neutralization to a highly homologous pre-emergent bat coronavirus, WIV1-CoV, which has not yet crossed the species barrier. These results highlight the importance of neutralizing humoral immunity on disease progression and the need to develop broadly protective interventions to prevent future coronavirus pandemics.

Phylogenetic Analysis of Spike and Envelope Proteins for a Number of Bat Coronaviruses for Understanding the Hypothesis of Possible Origin for the Novel 2019- nCoV

Coronavirus Disease 19 (COVID-19) emergence reveals globally a great health issue and due to the limited information and knowledge on the origin of this novel coronavirus 2019 (2019-nCoV). Therefore, this study aims to investigate the evolution and analysis of molecular epidemiology for both Spike and Envelope proteins of 20 available complete genome sequences of different bat coronaviruses including 2019-nCoV in order to find out which type of bat coronaviruses is more likely to be the origin of this new 2019-nCoV and also multiple amino acid sequences of Envelope protein for all bat coronaviruses were aligned for the purpose of finding the greater probability of novel 2019-nCoV original host among bat coronaviruses. Phylogenetic tree analysis for Spike protein revealed that all 2019-nCoV related coronaviruses isolated from these species of species are discovered in China and Hong Kong and the Middle East bat are less likely to contribute in spreading or to become the origin of 2019-nCoV and all coronaviruses that from Hong Kong and China are located into one clade next to the clade that contains 2019-nCoV coronaviruses which indicates that this group of coronaviruses are genetically different for 2019-nCoV; moreover, Hong Kong and USA bat coronaviruses does not contain the bat coronavirus from China and are located into one clade far from the clade that contains 2019-nCoV indicates that all coronaviruses are genetically very different from 2019-nCoV, and USA bat coronavirus may has no role in generating of 2019-nCoV. The phylogenetic trees analysis of Envelope protein showed that Envelope protein of different coronaviruses are more similar in comparison to Spike protein, USA bat coronavirus has a relatively closeness relationship to 2019-nCoV. Furthermore, Envelope protein alignment showed the closely related amino acid sequence which confirms that the outcomes of phylogenetic tree analysis in which that these bat coronaviruses have genetically close relationship together and more interestingly amino acid sequence (MG772934.1) shows 100% identity with the amino acid sequence of 2019-nCoV (NC 045512.2) and the same virus has a close relationship in both Spike and Envelope due to that in both phylogenetic tree analysis are neighbored with 2019-nCoV in the same clade.

On the role of viruses in nature and what this means for the COVID-19 pandemic.

On the role of viruses in nature and what this means for the COVID-19 pandemic.

Phylogenetic supertree reveals detailed evolution of SARS-CoV-2

Corona Virus Disease 2019 (COVID-19) caused by the emerged coronavirus SARS-CoV-2 is spreading globally. The origin of SARS-Cov-2 and its evolutionary relationship is still ambiguous. Several reports attempted to figure out this critical issue by genome-based phylogenetic analysis, yet limited progress was obtained, principally owing to the disability of these methods to reasonably integrate phylogenetic information from all genes of SARS-CoV-2. Supertree method based on multiple trees can produce the overall reasonable phylogenetic tree. However, the supertree method has been barely used for phylogenetic analysis of viruses. Here we applied the matrix representation with parsimony (MRP) pseudo-sequence supertree analysis to study the origin and evolution of SARS-CoV-2. Compared with other phylogenetic analysis methods, the supertree method showed more resolution power for phylogenetic analysis of coronaviruses. In particular, the MRP pseudo-sequence supertree analysis firmly disputes bat coronavirus RaTG13 be the last common ancestor of SARS-CoV-2, which was implied by other phylogenetic tree analysis based on viral genome sequences. Furthermore, the discovery of evolution and mutation in SARS-CoV-2 was achieved by MRP pseudo-sequence supertree analysis. Taken together, the MRP pseudo-sequence supertree provided more information on the SARS-CoV-2 evolution inference relative to the normal phylogenetic tree based on full-length genomic sequences.

Novel SARS-CoV-2 encoded small RNAs in the passage to humans.

MotivationThe Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) has recently emerged as the responsible for the pandemic outbreak of the coronavirus disease (COVID-19). This virus is closely related to coronaviruses infecting bats and Malayan pangolins, species suspected to be an intermediate host in the passage to humans. Several genomic mutations affecting viral proteins have been identified, contributing to the understanding of the recent animal-to-human transmission. However, the capacity of SARS-CoV-2 to encode functional putative microRNAs (miRNAs) remains largely unexplored.ResultsWe have used deep learning to discover 12 candidate stem-loop structures hidden in the viral protein-coding genome. Among the precursors, the expression of eight mature miRNAs-like sequences was confirmed in small RNA-seq data from SARS-CoV-2 infected human cells. Predicted miRNAs are likely to target a subset of human genes of which 109 are transcriptionally deregulated upon infection. Remarkably, 28 of those genes potentially targeted by SARS-CoV-2 miRNAs are down-regulated in infected human cells. Interestingly, most of them have been related to respiratory diseases and viral infection, including several afflictions previously associated with SARS-CoV-1 and SARS-CoV-2. The comparison of SARS-CoV-2 pre-miRNA sequences with those from bat and pangolin coronaviruses suggests that single nucleotide mutations could have helped its progenitors jumping inter-species boundaries, allowing the gain of novel mature miRNAs targeting human mRNAs. Our results suggest that the recent acquisition of novel miRNAs-like sequences in the SARS-CoV-2 genome may have contributed to modulate the transcriptional reprogramming of the new host upon infection.

Evolutionary dynamics and geographic dispersal of beta coronaviruses in African bats.

Bats have been shown to serve as reservoir host of various viral agents including coronaviruses. They have also been associated with the novel coronavirus SARS-CoV-2. This has made them an all important agent for CoV evolution and transmission. Our objective in this study was to investigate the dispersal, phylogenomics and evolution of betacoronavirus (βCoV) among African bats. We retrieved sequence data from established databases such as GenBank and Virus Pathogen Resource, covering the partial RNA dependent RNA polymerase (RdRP) gene of bat coronaviruses from eight African, three Asian, five European, two South American countries and Australia. We analyzed for phylogeographic information relating to genetic diversity and evolutionary dynamics. Our study revealed that majority of the African strains fell within Norbecovirus subgenera, with an evolutionary rate of 1.301 × 10−3, HPD (1.064 × 10−3–1.434 × 10−3) subs/site/year. The African strains diversified into three main subgenera, Norbecovirus, Hibecovirus and Merbecovirus. The time to most common recent ancestor for Norbecovirus strains was 1973, and 2007, for the African Merbecovirus strains. There was evidence of inter species transmission of Norbecovirus among bats in Cameroun and DRC. Phlylogeography showed that there were inter-continental spread of Bt-CoV from Europe, China and Hong Kong into Central and Southern Africa, highlighting the possibility of long distance transmission. Our study has elucidated the possible evolutionary origins of βCoV among African bats; we therefore advocate for broader studies of whole genome sequences of BtCoV to further understand the drivers for their emergence and zoonotic spillovers into human population.

Conserved Genomic Terminals of SARS-CoV-2 as Coevolving Functional Elements and Potential Therapeutic Targets.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 40 million people worldwide, with over 1 million deaths as of October 2020 and with multiple efforts in the development and testing of antiviral drugs and vaccines under way. In order to gain insights into SARS-CoV-2 evolution and drug targets, we investigated how and to what extent the SARS-CoV-2 genome sequence differs from those of other well-characterized human and animal coronavirus genomes, as well as how polymorphic SARS-CoV-2 genomes are generally. We ultimately sought to identify features in the SARS-CoV-2 genome that may contribute to its viral replication, host pathogenicity, and vulnerabilities. Our analyses suggest the presence of unique sequence signatures in the 3' untranslated region (3'-UTR) of betacoronavirus lineage B, which phylogenetically encompasses SARS-CoV-2 and SARS-CoV as well as multiple groups of bat and animal coronaviruses. In addition, we identified genome-wide patterns of variation across different SARS-CoV-2 strains that likely reflect the effects of selection. Finally, we provide evidence for a possible host-microRNA-mediated interaction between the 3'-UTR and human microRNA hsa-miR-1307-3p based on the results of multiple computational target prediction analyses and an assessment of similar interactions involving the influenza A H1N1 virus. This interaction also suggests a possible survival mechanism, whereby a mutation in the SARS-CoV-2 3'-UTR leads to a weakened host immune response. The potential roles of host microRNAs in SARS-CoV-2 replication and infection and the exploitation of conserved features in the 3'-UTR as therapeutic targets warrant further investigation.IMPORTANCE The coronavirus disease 2019 (COVID-19) outbreak is having a dramatic global effect on public health and the economy. As of October 2020, SARS-CoV-2 has been detected in over 189 countries, has infected over 40 million people, and is responsible for more than 1 million deaths. The genome of SARS-CoV-2 is small but complex, and its functions and interactions with human host factors are being studied extensively. The significance of our study is that, using extensive SARS-CoV-2 genome analysis techniques, we identified potential interacting human host microRNA targets that share similarity with those of influenza A virus H1N1. Our study results will allow the development of virus-host interaction models that will enhance our understanding of SARS-CoV-2 pathogenesis and motivate the exploitation of both the interacting viral and host factors as therapeutic targets.

Novel viruses detected in bats in the Republic of Korea

Bats are natural reservoirs for potential zoonotic viruses. In this study, next-generation sequencing was performed to obtain entire genome sequences of picornavirus from a picornavirus-positive bat feces sample (16BF77) and to explore novel viruses in a pooled bat sample (16BP) from samples collected in South Korea, 2016. Fourteen mammalian viral sequences were identified from 16BF77 and 29 from 16BP, and verified by RT-PCR. The most abundant virus in 16BF77 was picornavirus. Highly variable picornavirus sequences encoding 3Dpol were classified into genera Kobuvirus, Shanbavirus, and an unassigned group within the family Picornaviridae. Amino acid differences between these partial 3Dpol sequences were ≥ 65.7%. Results showed that one bat was co-infected by picornaviruses of more than two genera. Retrovirus, coronavirus, and rotavirus A sequences also were found in the BP sample. The retrovirus and coronavirus genomes were identified in nine and eight bats, respectively. Korean bat retroviruses and coronavirus demonstrated strong genetic relationships with a Chinese bat retrovirus (RfRV) and coronavirus (HKU5-1), respectively. A co-infection was identified in one bat with a retrovirus and a coronavirus. Our results indicate that Korean bats were multiply infected by several mammal viruses.

Static all-atom energetic mappings of the SARS-Cov-2 spike protein and dynamic stability analysis of "Up" versus "Down" protomer states.

The SARS-CoV-2 virion responsible for the current world-wide pandemic COVID-19 has a characteristic Spike protein (S) on its surface that embellishes both a prefusion state and fusion state. The prefusion Spike protein (S) is a large trimeric protein where each protomer may be in a so-called Up state or Down state, depending on the configuration of its receptor binding domain (RBD) within its distal, prefusion S1 domain. The Up state is believed to allow binding of the virion to ACE-2 receptors on human epithelial cells, whereas the Down state is believed to be relatively inactive or reduced in its binding behavior. We have performed detailed all-atom, dominant energy landscape mappings for noncovalent interactions (charge, partial charge, and van der Waals) of the SARS-CoV-2 Spike protein in its static prefusion state based on two recent and independent experimental structure publications. We included both interchain interactions and intrachain (domain) interactions in our mappings in order to determine any telling differences (different so-called “glue” points) between residues in the Up and Down state protomers. The S2 proximal, fusion domain demonstrated no appreciable energetic differences between Up and Down protomers, including interchain as well as each protomer’s intrachain, S1-S2 interactions. However, the S1 domain interactions across neighboring protomers, which include the RBD-NTD cross chain interactions, showed significant energetic differences between Up-Down and Down-Down neighboring protomers. This included, for example, a key RBD residue ARG357 in the Up-Down interaction and a three residue sequence ALA520-PRO521-ALA522, associated with a turn structure in the RBD of the Up state protomer, acting as a stabilizing interaction with the NTD of its neighbor protomer. Additionally, our intra chain dominant energy mappings within each protomer, identified a significant “glue” point or possible “latch” for the Down state protomer between the S1 subdomain, SD1, and the RBD domain of the same protomer that was completely missing in the Up state protomer analysis. Ironically, this dominant energetic interaction in the Down state protomer involved the backbone atoms of the same three residue sequence ALA520-PRO521-ALA522 of the RBD with the amino acid R-group of GLN564 in the SD1 domain. Thus, this same three residue sequence acts as a stabilizer of the RBD in the Up conformation through its interactions with its neighboring NTD chain and a kind of latch in the Down state conformation through its interactions with its own SD1 domain. The dominant interaction energy residues identified here are also conserved across reported variations of SARS-CoV-2, as well as the closely related virions SARS-Cov and the bat corona virus RatG13. We conducted preliminary molecular dynamics simulations across 0.1 μ seconds to see if this latch provided structural stability and indeed found that a single point mutation (Q564G) resulted in the latch releasing transforming the protomer from the Down to the Up state conformation. Full trimeric Spike protein studies of the same mutation across all protomers, however, did not exhibit latch release demonstrating the critical importance of interchain interactions across the S1 domain, including RBD-NTD neighboring chain interactions. Therapies aimed at disrupting these noncovalent interactions could be a viable route for the physico-chemical mitigation of this deadly virion.

SARS-CoV-2 infection and phylogenetic analysis with the risk factors in human body alongside the pulmonary effects and medication

Related the extremely transmittable abilities of SARS-CoV-2,a harmonious virus to the bat CoV, gets transmitted by three principal processes-- the inhalation of droplets from the SARS-CoV-2 infected person, contacting to the person, and by the surfaces and materials defiled with the virus. Whereupon bat Coronavirus is mostly like the pandemic causing virus SARS-CoV-2, bats are often deliberated and figured out as a possible primary host although no intermediate has not been defined yet in the wherewithal of transmission. The Spike Glycoprotein plays an important role in the case of penetration with the assistance of the ACE2 receptor and the Receptor Binding Domain. In the human body, infiltrating the nucleic acid into host cells, SARS-CoV-2 attacks one cell and one by one into the whole human body; therefore, infected cases are found symptomatic and asymptomatic considering the immune power. Patients with cardiovascular disease or diabetes proceed with their treatment with ACE2 often; therefore, there might be a high chance of getting infected. Whereas the SARS-CoV-2 infects the blood and then lungs, Antigens improvement can be better in order to avoid high-complicated effects. Currently, no vaccination or no accurate cure and treatment has not been defined. An explanation with analysis on SARS-CoV-2 has been performed from the aspect of virology, immunology and molecular biology. Several relevant figures have been included hereby in order to a better understanding of the very concept.

New putative animal reservoirs of SARS-CoV-2 in Italian fauna: A bioinformatic approach

SARS-CoV-2 is a virus belonging to the betacoronavirus family, causing fatal respiratory disease in humans, which became pandemic in 2020. Italy is one of the most affected countries by COVID-19, particularly in the northern regions. Several studies consider COVID-19 a zoonotic disease and, since Italy is the repository of a high biodiversity, SARS-CoV-2 infection in animals can be considered as a reservoir of the virus or favor the spreading between animals and humans. In this work, we analyzed the amino acid sequences of ACE2 protein of the most common domestic and wild animals present in Italy. Among the latter, we focused on ACE2 of the Chiroptera species present in Italy to identify the primary reservoir in this region. First, we reproduced in silico the Chiroptera ACE2/viral spike (S) protein interactions on the human ACE2/SARS-CoV-2 S complex model and identified the critical residues for the binding. In silico molecular docking of ACE2 belonging to Chiroptera vs SARS-CoV-2 S protein pointed to Rhinolophus ferrumequinum as a bat living in Italy, that may be a potential primary reservoir of the virus. On the other hand, a sequence similarity search on ACE2 of domestic and wild animals living in Italy pointed to domestic (horses, cats, cattle and sheep) and wild (European rabbits and grizzly bears) animal species as potential SARS-CoV-2 secondary reservoirs. Molecular docking of ACE2 belonging to these species vs S protein of Bat coronavirus (Bt-CoV/Rp3/2004) suggests that the primary reservoir Rhinolophus ferrumequinum may infect the secondary reservoirs, domestic and worldwide animals living in Italy, determining a specific risk of SARS-CoV-2 infection.

Spillover: the role of bats and relationships as reservoirs of zoonotic viruses and the origin of new coronaviruses

Since recent findings on coronavirus, there are numerous outstanding questions about the recent emergence of these viruses, their relationship to bats, environmental issues, gene recombinations, reservoirs, evolution and the role of human coronavirus in human infection. This review aimed to gather information about the possible origin of the new coronavirus (SARS-CoV-2) and its relationship with the alated mammals and the new strains found. Selected studies indicate that SARS-CoV-2 is a chimeric virus between a bat coronavirus and a coronavirus of unknown origin. One of the possibilities points to bats as being a reservoir originating from SARS-CoV-2 (COVID-19), transmitting to man via host source. The records indicate that a recombination between the coronaviruses of pangolins and the bat coronavirus BatCoV RaTG13 and SARS-CoV-2 human there is a common ancestry among these Betacoronaviruses, which were even identified in other mammalian species, named Ptajacu-CoV. Several questions were raised about the artificial origin of the virus by laboratory manipulation. However, although remote, further investigations are needed to rule out a probable release and the real existence of SARS-CoV-2 and beta coronaviruses, which circulate for decades among the human species.

SARS-CoV-2 and Three Related Coronaviruses Utilize Multiple ACE2 Orthologs and Are Potently Blocked by an Improved ACE2-Ig.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has caused >20 million infections and >750,000 deaths. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, has been found closely related to the bat coronavirus strain RaTG13 (Bat-CoV RaTG13) and a recently identified pangolin coronavirus (Pangolin-CoV-2020). Here, we first investigated the ability of SARS-CoV-2 and three related coronaviruses to utilize animal orthologs of angiotensin-converting enzyme 2 (ACE2) for cell entry. We found that ACE2 orthologs of a wide range of domestic and wild mammals, including camels, cattle, horses, goats, sheep, cats, rabbits, and pangolins, were able to support cell entry of SARS-CoV-2, suggesting that these species might be able to harbor and spread this virus. In addition, the pangolin and bat coronaviruses, Pangolin-CoV-2020 and Bat-CoV RaTG13, were also found able to utilize human ACE2 and a number of animal-ACE2 orthologs for cell entry, indicating risks of spillover of these viruses into humans in the future. We then developed potently anticoronavirus ACE2-Ig proteins that are broadly effective against the four distinct coronaviruses. In particular, through truncating ACE2 at its residue 740 but not 615, introducing a D30E mutation, and adopting an antibody-like tetrameric-ACE2 configuration, we generated an ACE2-Ig variant that neutralizes SARS-CoV-2 at picomolar range. These data demonstrate that the improved ACE2-Ig variants developed in this study could potentially be developed to protect from SARS-CoV-2 and some other SARS-like viruses that might spillover into humans in the future.IMPORTANCE The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the currently uncontrolled coronavirus disease 2019 (COVID-19) pandemic. It is important to study the host range of SARS-CoV-2, because some domestic species might harbor the virus and transmit it back to humans. In addition, insight into the ability of SARS-CoV-2 and SARS-like viruses to utilize animal orthologs of the SARS-CoV-2 receptor ACE2 might provide structural insight into improving ACE2-based viral entry inhibitors. In this study, we found that ACE2 orthologs of a wide range of domestic and wild animals can support cell entry of SARS-CoV-2 and three related coronaviruses, providing insights into identifying animal hosts of these viruses. We also developed recombinant ACE2-Ig proteins that are able to potently block these viral infections, providing a promising approach to developing antiviral proteins broadly effective against these distinct coronaviruses.

Coronaviruses in Brazilian bats: A matter of concern?

Coronaviruses in Brazilian bats: A matter of concern?

Sequence Analysis and Structure Prediction of SARS-CoV-2 Accessory Proteins 9b and ORF14: Evolutionary Analysis Indicates Close Relatedness to Bat Coronavirus.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a single-stranded RNA genome that encodes 14 open reading frames (ORFs), eight of which encode accessory proteins that allow the virus to infect the host and promote virulence. The genome expresses around 29 structural and nonstructural protein products. The accessory proteins of SARS-CoV-2 are not essential for virus replication but do affect viral release, stability, and pathogenesis and finally contribute to virulence. This paper has attempted the structure prediction and functional analysis of two such accessory proteins, 9b and ORF14, in the absence of experimental structures. Sequence analysis, structure prediction, functional characterization, and evolutionary analysis based on the UniProtKB reviewed the amino acid sequences of SARS-CoV-2 9b (P0DTD2) and ORF14 (P0DTD3) proteins. Modeling has been presented with the introduction of hybrid comparative and ab initio modeling. QMEANDisCo 4.0.0 and ProQ3 for global and local (per residue) quality estimates verified the structures as high quality, which may be attributed to structure-based drug design targets. Tunnel analysis revealed the presence of 1-2 highly active tunneling sites, perhaps which will able to provide certain inputs for advanced structure-based drug design or to formulate potential vaccines in the absence of a complete experimental structure. The evolutionary analysis of both proteins of human SARS-CoV-2 indicates close relatedness to the bat coronavirus. The whole-genome phylogeny indicates that only the new bat coronavirus followed by pangolin coronaviruses has a close evolutionary relationship with the novel SARS-CoV-2.

A Crowned Killer's Résumé: Genome, Structure, Receptors, and Origin of SARS-CoV-2.

The recent emergence and rapid global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pose an unprecedented medical and socioeconomic crisis, and the disease caused by it, Coronavirus disease 2019 (COVID-19), was declared a pandemic by the World Health Organization (WHO) on March 11, 2020. Chinese scientists and physicians rapidly identified the causative pathogen, which turned out to be a novel betacoronavirus with high sequence similarities to bat and pangolin coronaviruses. The scientific community has ignited tremendous efforts to unravel the biological underpinning of SARS-CoV-2, which constitutes the foundation for therapy and vaccine development strategies. Here, we summarize the current state of knowledge on the genome, structure, receptor, and origin of SARS-CoV-2.

A systematic review of etiology, epidemiology, clinical manifestations, image findings, and medication of 2019 Corona Virus Disease-19 in Wuhan, China.

Background:Unknown origin pneumonia has been furiously spreading since the late of December 2019, subsequently spread to approximately all provinces and areas in China and many countries, which was announced as a Public Health Emergency of International Concern by World Health Organization (WHO). The studies on 2019 Corona Virus Disease-19 (COVID-19) conducted from various fields around the world. Herein, the objective of the present study is to summarize the etiology, epidemiology, clinical manifestations, image findings, traceability analysis, and drug development of COVID-19.Methods:The following electronic databases were searched: Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database, VIP Chinese Science and Technology Periodical Database, and Wanfang Data. Other relevant literature will be manually searched as a compliment. We have reviewed etiology, epidemiology, clinical manifestations, image findings, and medication from case reports and retrospective clinical studies relating to COVID-19 published since the outbreak.Results:The coronavirus is closely related to bat coronavirus and pangolin coronavirus. Besides, the infection pathway is confirmed to be the respiratory and digestive systems. The virus indicates person-to-person transmission and some patients present asymptomatic. The elderly have a higher mortality rate. Rapid and sensitive nucleic acid testing is usually used as a basis for diagnosis. Currently, there is no specific vaccine and antiviral drug. Intervention actions such as travel bans and quarantine adopted have effectively reduced the spread of the epidemic.Conclusion:This systemic review will provide high-quality evidence to summarize etiology, epidemiology, clinical manifestations, image findings, traceability analysis, drug development in patients with COVID-19.

Coronavirus (COVID-19) Symptoms, Treatment, and Recent Medical Challenges to the World: A Review

Coronavirus infections have emerged as epidemic and pandemic threats throughout the world. Severe acute respiratory syndrome coronavirus (SARS-CoV-2) has spread across 203 countries and territories in all 5 major continents. World Health Organization (WHO) declared this as a public health emergency of international concern on January 30, 2020. Subsequently, on February 11, 2020, a new name was given to this disease i.e. COVID-19 by an expert group from WHO. As of 3:37 pm CEST, 14 August 2020, there have been 20,730,456 confirmed cases of COVID-19, including 751,154 deaths, reported to WHO. It possibly originated from a small animal market in Wuhan, China. A cluster of patients was admitted with unusual pneumonia not responding to treatment in various hospitals. Epidemiological, genomic analysis and correlation with other coronaviruses led to the isolation of new coronavirus, closely resembling the bat coronaviruses, from such patients in Wuhan. They were identified as the SARS-CoV-2. This virus infection presents an influenza-like illness in the affected people. Fever, cough, respiratory distress with fatigue, diarrhea, nausea, and vomiting are common symptoms seen in adults. The transmissibility of SARS-CoV-1 was less as compared to SARS-CoV-2 infection, and it was well controlled with good public health efforts. The present COVID-19 epidemic is still in the acceleration phase of 3 and 4 in various countries. Without any effective antiviral agents available at present, the need of the hour is early case detection, isolation of cases, use of good preventive care measures by the household contacts and in the hospital setup. Here, we have placed the symptoms and treatment schemes for the COVID-19 from the practice of different research organizations of the World including WHO.