Caused Coronavirus Disease 2019 Research Articles

Comparative Atlas of SARS-CoV-2 Substitution Mutations: A Focus on Iranian Strains Amidst Global Trends.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new emerging coronavirus that caused coronavirus disease 2019 (COVID-19). Whole-genome tracking of SARS-CoV-2 enhanced our understanding of the mechanism of the disease, control, and prevention of COVID-19. we analyzed 3368 SARS-CoV-2 protein sequences from Iran and compared them with 15.6 million global sequences in the GISAID database, using the Wuhan-Hu-1 strain as a reference. Our investigation revealed that NSP12-P323L, ORF9c-G50N, NSP14-I42V, membrane-A63T, Q19E, and NSP3-G489S were found to be the most frequent mutations among Iranian SARS-CoV-2 sequences. Furthermore, it was observed that more than 94% of the SARS-CoV-2 genome, including NSP7, NSP8, NSP9, NSP10, NSP11, and ORF8, had no mutations when compared to the Wuhan-Hu-1 strain. Finally, our data indicated that the ORF3a-T24I, NSP3-G489S, NSP5-P132H, NSP14-I42V, envelope-T9I, nucleocapsid-D3L, membrane-Q19E, and membrane-A63T mutations might be responsible factors for the surge in the SARS-CoV-2 Omicron variant wave in Iran. real-time genomic surveillance is crucial for detecting new SARS-CoV-2 variants, updating diagnostic tools, designing vaccines, and understanding adaptation to new environments.

SARS-CoV-2: Prediction of critical ionic amino acid mutations

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that caused coronavirus disease 2019 (COVID-19), has been studied thoroughly, and several variants are revealed across the world with their corresponding mutations. Studies and vaccines development focus on the genetic mutations of the S protein due to its vital role in allowing the virus attach and fuse with the membrane of a host cell. In this perspective, we study the effects of all ionic amino acid mutations of the SARS-CoV-2 viral spike protein S1 when bound to Antibody CC12.1 within the SARS-CoV-2:CC12.1 complex model. Binding free energy calculations between SARS-CoV-2 and antibody CC12.1 are based on the Analysis of Electrostatic Similarities of Proteins (AESOP) framework, where the electrostatic potentials are calculated using Adaptive Poisson-Boltzmann Solver (APBS). The atomic radii and charges that feed into the APBS calculations are calculated using the PDB2PQR software. Our results are the first to propose in silico potential life-threatening mutations of SARS-CoV-2 beyond the present mutations found in the five common variants worldwide. We find each of the following mutations: K378A, R408A, K424A, R454A, R457A, K458A, and K462A, to play significant roles in the binding to Antibody CC12.1, since they are turned into strong inhibitors on both chains of the S1 protein, whereas the mutations D405A, D420A, and D427A, show to play important roles in this binding, as they are turned into mild inhibitors on both chains of the S1 protein.

After action review of the COVID-19 pandemic response in North West province, South Africa.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused coronavirus disease 2019 (COVID-19) pandemic with major disruptions globally. Northwest Province Department of Health (NWDoH) in South Africa set up comprehensive epidemiological emergency response plans for preventing, finding, containing and stopping the spread of COVID-19 in accordance with the National Disaster Management Act. This After-Action Report (AAR) describes the provincial response to the pandemic from September 2020 to October 2022. The AAR was conducted using the World Health Organization AAR methodology. Focus groups discussed five items: coordination, leadership and governance; epidemiology, surveillance and laboratory; case management and continuity of essential services; risk communication and community engagement and COVID-19 vaccination. The timely establishment and activation of provincial intergovernmental and intersectoral coordinating structures led to effective coordination, resource mobilisation, leadership, decision-making and intervention. The effective communication in the department and other stakeholders resulted in improved surveillance data quality, timelier response and increased ownership of data. Dissemination, training and implementation of case management protocols ensured standardised case management. The multi-channel information dissemination targeting different audiences empowered people with real-time knowledge on the infection and encouraged health-seeking behaviours. The AAR demonstrated the importance of coordinated epidemiological, laboratory and communication response that requires significant public health reserve capacity in peacetime for rapid expansion in an emergency. This review contributes to the body of knowledge emerging from the COVID-19 pandemic and provides guidance on enhanced public health response to future emergencies.

SARS-CoV-2 subgenomic RNA: formation process and rapid molecular diagnostic methods.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which caused coronavirus disease-2019 (COVID-19) is spreading worldwide and posing enormous losses to human health and socio-economic. Due to the limitations of medical and health conditions, it is still a huge challenge to develop appropriate discharge standards for patients with COVID-19 and to use medical resources in a timely and effective manner. Similar to other coronaviruses, SARS-CoV-2 has a very complex discontinuous transcription process to generate subgenomic RNA (sgRNA). Some studies support that sgRNA of SARS-CoV-2 can only exist when the virus is active and is an indicator of virus replication. The results of sgRNA detection in patients can be used to evaluate the condition of hospitalized patients, which is expected to save medical resources, especially personal protective equipment. There have been numerous investigations using different methods, especially molecular methods to detect sgRNA. Here, we introduce the process of SARS-CoV-2 sgRNA formation and the commonly used molecular diagnostic methods to bring a new idea for clinical detection in the future.

Myocarditis in SARS-CoV-2: A Meta-Analysis.

There has been a rise in cardiovascular events following the onset of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a strain that caused coronavirus disease 2019 (COVID-19). Although rare, there has been an increase in reports of myocarditis secondary to both individuals infected by the strain and those who received the COVID-19 mRNA vaccine. The focus of this study is to determine the risk of myocarditis associated with the COVID-19 vaccine and SARS-CoV-2 infection. Relevant literature was collected using the search engines PubMed, Google Scholar, and the WHO Global Literature on Coronavirus Disease. Randomized controlled clinical trials and cohort studies reporting the risk of myocarditis induced by SARS-CoV-2 infection and COVID-19 vaccines were used. A meta-analysis was conducted using the inverse variance method using RevMan application software. A meta-analysis of the compiled data showed a mean risk ratio of 4.74 (95% confidence interval (CI) = 2.40 to 9.36; p < 0.0000100), which indicates there is a significant difference in the risk of COVID-19-induced myocarditis in those with unspecified vaccination status compared to the non-infected population. A meta-analysis of the selected data found a mean risk ratio of 5.01 (95% CI = 4.14 to 6.08; p < 0.0000100), indicating a significant difference in the risk of COVID-19-induced myocarditis between those who are unvaccinated and the non-infected population. Upon a meta-analysis of the selected data set, a mean risk ratio of2.55 (95% CI = 0.840 to 7.74; p = 0.100) was found, indicating no significant difference in the risk of vaccine-induced myocarditis between those with a vaccinated vaccination status and that of the non-infected population. The result of this meta-analysis showed that infection with SARS-CoV-2 in unvaccinated patients carries a statistically significant increased risk of acquiring myocarditis while those receiving the vaccination do not share this same risk.

Clinical Characteristics, Diagnosis, and Therapeutics of COVID-19: A Review.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that suddenly emerged at the end of December 2019 and caused coronavirus disease 2019 (COVID-19) continues to afflict humanity, not only seriously affecting healthcare systems but also leading to global social and economic imbalances. As of August 2022, there were approximately 580 million confirmed cases of COVID-19 and approximately 6.4 million confirmed deaths due to this disease. The data are sufficient to highlight the seriousness of SARS-CoV-2 infection. Although most patients with COVID-19 present primarily with respiratory symptoms, an increasing number of extrapulmonary systemic symptoms and manifestations have been associated with COVID-19. Since the outbreak of COVID-19, much has been learned about the disease and its causative agent. Therefore, great effort has been aimed at developing treatments and drug interventions to treat and reduce the incidence of COVID-19. In this narrative review, we provide a brief overview of the epidemiology, mechanisms, clinical manifestations, diagnosis, and therapeutics of COVID-19.

Maternal SARS‐CoV‐2 infection: The potential vertical transmission of SARS‐CoV‐2 and impact on neonates: A review

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), a large, lipid‐enveloped, single‐stranded RNA virus, is a highly contagious virus that caused coronavirus disease 2019 (COVID‐19), declared a pandemic by the World Health Organization on March 11, 2020. Pregnant women are usually considered at high risk for infectious diseases, including COVID‐19. Maternal SARS‐CoV‐2 infection can adversely affect the pregnancy and birth outcomes, such as abortion, intrauterine growth restriction, and prematurity. Some meta‐analysis suggested that the outcomes of newborns are different between symptomatic and asymptomatic pregnant women but similar in asymptomatic and SARS‐CoV‐2 negative group. Maternal infection increases the risk of vertical transmission; also the presence of SARS‐CoV‐2 or its RNA in maternal samples in some case reports raised the possibility of intrauterine transmission. Also, contact transmission during delivery and postnatal transmission are discussed. Although most infected newborns are asymptomatic or mildly symptomatic, there are case reports of severe neonatal SARS‐CoV‐2 infection, including cardiorespiratory failure and death. Otherwise, some studies suggested that the COVID‐19 pandemic was associated with a reduction for preterm birth during the pandemic compared with the prepandemic period. We conduct this review to try to make a conclusion about the vertical transmission of SARS‐CoV‐2 and impact on neonates due to Maternal SARS‐CoV‐2 infection.

Cardiac Troponin-I and COVID-19: a prognostic tool for in-hospital mortality

ABSTRACT Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused Coronavirus disease 2019 (COVID-19) emerging outbreak. In up to 15% of cases, the clinical course of the disease may get complicated to a severe form of interstitial pneumonia, acute respiratory distress syndrome (ARDS) and/or multi-organ failure (MOF) and death. So, our cross-sectional study was conducted to evaluate cardiac troponin I as a prognostic factor for poor in-hospital outcome in patients admitted with COVID-19 infection. Methods Study included 101 confirmed COVID-19 patients with age > 18 years old, of any gender, survivors (74 patients) and non-survivors (27 patients), with no history of any cardiac or pulmonary disease. They were subjected to medical history, clinical examination and laboratory investigations including cardiac troponin I, CBC, urea, creatinine, AST, ALT, CRP, D-Dimer, INR, Na, K and ABG. During their hospital stay, a comparison was done among all sociodemographic data, vital signs on admission, laboratory findings including troponin I level, clinical outcome (need for mechanical ventilation and length of mechanical ventilation if needed), CT chest, CORADS score and APACHI II score between both groups. Results The mean troponin levels showed statistically significant difference between COVID-19 survivors and non-survivors (P-value = 0.001). Significant lower number of survivors needed mechanical ventilation compared to the non survivors (p-value <0.001). The non-survivors group has significantly higher APACHE II score compared to the survivors group (p-value <0.001). At the cutoff point of 0.65 the sensitivity of troponin I as a predictor of mortality in COVID-19 patients is 63.0% and the specificity is 90.5%. Conclusion Cardiac Troponin I is a good prognostic factor for poor in-hospital outcomes among COVID-19 patients; it can predict the need for mechanical ventilation and the in-hospital mortality, however it couldn’t predict the length of mechanical ventilation among those patients.

Infection Control Practices in In-Center Hemodialysis Units During Wave 1 of the COVID-19 Pandemic in Ontario, Canada: Research Letter.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus that caused coronavirus disease 2019 (COVID-19), the multisystem disease central to the COVID-19 pandemic. As patients receiving in-center maintenance hemodialysis require treatment 3 times weekly, they were unable to fully isolate. It was important for in-center hemodialysis units to implement robust infection control practices to ensure patient safety and minimize risk of transmitting SARS-CoV-2 among patients and staff. There are 27 renal programs within Ontario, Canada, providing care for about 9000 people across about 100 in-center hemodialysis units. These units are funded by the Ontario Renal Network (ORN), which is part of the provincial agency Ontario Health. The objective was to track infection control practices that were implemented by in-center hemodialysis units and be able to provide a descriptive narrative of the COVID-19 pandemic response of Ontario's hemodialysis units between March and September 2020. Between May and September 2020, data were collected from Ontario's 27 renal programs on the implementation of key infection control practices, including symptom screening, use of personal protective equipment, testing, practices specifically related to patients from congregate living settings, other prevention practices, and outbreak management. There were 4 data collection cycles, each approximately 1 month apart. The results were compiled and shared across the province, and infection control practices were also discussed at provincial COVID-19 teleconferences hosted by the ORN. By March 2020, all but one renal program had implemented one or more forms of symptom screening, all renal programs had implemented physical distancing in waiting rooms and restricted visitors, and 74% of renal programs had implemented universal masking for all staff. By April 2020, 89% of renal programs had implemented universal masking for all patients, 52% had implemented enhanced contact and droplet precautions for suspected or positive cases, and 59% of renal programs tested all patients from congregate living settings regularly (with a low symptom threshold for testing). Infection control practices became more homogeneous across renal programs over time, and most practices were in place as of the last data collection. The renal system in Ontario was able to respond quickly within the first 2 months of the pandemic to minimize the spread of COVID-19 within in-center hemodialysis units. Through provincial teleconferences, infection control practices were shared across the province as the pandemic and hemodialysis unit responses evolved. This supported renal programs to advocate locally if their hospital was lagging in practices felt to be of value in other hemodialysis units. Although no direct correlation can be made regarding the implementation of infection control practices within in-center hemodialysis units and the number of COVID-19 cases in this population, the limited number of outbreaks in hemodialysis units may have been influenced by the proactive response of renal programs. Practices described in this article may support management and response to subsequent waves of COVID-19 or future similar infectious diseases.

The Association of Elevated Levels of LDH and CK-MB with Cardiac Injury and Mortality in COVID-19 Patients

Background: A new type of beta-coronavirus, named acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused coronavirus disease 2019 (COVID-19). Although COVID-19 is primarily associated with respiratory symptoms, cardiovascular complications can also occur. Herein, we aimed to evaluate whether the serum levels of enzymes related to cardiac injury, lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB), may associate with the mortality of COVID-19 patients to provide new insights to enhance clinical care. Methods: Based on hospital information systems (HIS) and patient records, we have retrospectively extracted laboratory findings of 159 patients with confirmed COVID-19 disease. The data of LDH and CK-MB of patients were defined as the day onset when the patients were admitted to the hospital. Results: The average age of all patients was almost 62 years old; the mean age in dead patients and recovered patients were 70 and 55 years old, respectively. The average aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine phosphokinase (CPK) values were 91.74, 66.20 U/L, and 268.24 U/L, respectively in all patients. The average LDH was 758.69 U/L, and CK-MB was 39.87 U/L in all of the COVID-19 patients. Among all 140 patients, laboratory results revealed that 121 (86.4%) patients had an elevated LDH level. In total, for 159 patients, the results indicated that 114 (71.69%) patients had an elevated CK-MB value. The average LDH value in dead patients was 1012.22 U/L, while in recovered patients was 545.20 U/L (P&lt;0.0001). Also, the average CK-MB level in dead patients was 60.84 U/L, while in recovered patients was 35.17 U/L (P=00.0026). Conclusion: Elevated levels of LDH and CK-MB following COVID-19 disease increase the risk of death in these patients.

Barotrauma in a Previously Healthy and Young COVID-19 Patient: an Autopsy Case Report

Abstract Introduction/Objective Since the emergence of a novel SARS-CoV-2 virus caused coronavirus disease 2019 (COVID-19), a great number of autopsy studies have been published. However, histopathologic studies focused on pulmonary barotrauma are very rare. Here we report an autopsy confined to the lungs on a young COVID-19 patient. Methods/Case Report The patient was a 37-year-old male, non-smoker, with no significant past medical history, and a body mass index of 24.1, who presented with shortness of breath and cough. A computerized tomography (CT) showed features of atypical pneumonia. The main abnormal laboratory data included elevated partial thromboplastin time, fibrinogen, and D-Dimer. The patient had been on mechanical ventilation for 35 days, and was complicated by recurrent pneumothoraces, hypotension, and worsening hypoxia. An autopsy limited to the lungs was performed after the patient expired. Grossly, the lungs showed increased weight, adhesions on visceral pleural surface, patchy consolidation and dilated subpleural cysts. Histological examination revealed cystically dilated/remodeled airspaces with extensive coagulative necrosis, focal alveolar hemorrhage and edema, focal confluent fibrosis, and subpleural blebs. Fresh fibrinous thrombi were seen in small- and medium-sized vessels. Viral cytopathic changes or significant inflammation were not observed. The findings in the lungs were consistent with barotrauma in COVID-19. Results (if a Case Study enter NA) NA. Conclusion This case demonstrates various histopathologic changes of the lungs in a previously healthy and young COVID-19 patient with prolonged hospital course of mechanical ventilation. The features of diffuse alveolar damage with inflammation usually seen in the early stage of barotrauma are not identified. Our findings in the lungs may represent the histopathologic characteristics of the later stage of barotrauma in COVID-19.

Measurement of the serum level of Elabela for the early detection of acute kidney injury in hospitalized Iraqi COVID-19 patients

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is caused coronavirus disease2019 (COVID-19) affecting people worldwide. The angiotensin converting enzyme2 (ACE2) represents areceptor of SARS-CoV-2 on the infected host cell. Apelin or its receptor agonists suppress the production ofangiotensin-converting enzyme (ACE) and angiotensin II (Ang-II) and is characterized by a protective effectagainst SARS-CoV-2.Objective: The study aims to assess the serum level of Elabela biomarker as an early detector for AcuteKidney Injury (AKI) in patients with COVID-19.Cases and Methods: This is a case-control study which included 45 hospitalized adult patients in multiplecenters (public hospitals) receiving COVID-19 cases in Baghdad. These cases had a positive real-time orreverse transcription polymerase chain reaction (RT-PCR) of nasal/oropharyngeal swabs. Excluded from thestudy were those with a negative PCR and comorbidities and 43 apparently healthy adult subjects as controls.The age range of the cases and controls was (20 to 60) yearsResult: There are no a statistically significant differences between the two groups in terms of age and genderdistribution. Statistically significant differences were found in terms of eGFR, S. Creatinine, D. dimer,NEU×103/µL, LYM×103/µL and ELA biomarker. Significant negative correlations were found betweenElabela with D. dimer and NEU×103/µL, and between eGFR with S. creatinine, D. Dimer, and NUT×103/µL.Conclusion: The Elabela biomarker can be used for the early detection of acute kidney injury in COVID-19patients.

Pengembangan Sistem Pendeteksi Masker Sesuai Protokol Kesehatan dengan Algoritma Mobilenetv2 dan Raspberry Pi

A new type of human coronavirus was discovered in December 2019 in Wuhan, China. In humans, coronaviruses usually cause respiratory tract infections, ranging from the common cold to serious diseases such as Middle East Respiratory (MERS) and Severe Acute Respiratory Syndrome (SARS). This new type of coronavirus was later named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV2) and caused Coronavirus Disease-2019 (COVID-19). COVID-19 can cause mild to severe symptoms. So, wearing a mask and keeping a distance is very important to stop the spread of COVID-19. In previous research, a deep learning model has been developed to identify whether the person is wearing a mask or not. In previous studies, the classification was limited to whether humans wore masks or not. There is no classification as to whether the use of masks is right or wrong and whether the masks worn are masks that are in accordance with the recommendations of the Ministry of Health. So that in this study, the detection system for the use of masks is able to detect the use of masks in accordance with the recommendations of the Indonesian Ministry of Health which refers to the interim WHO Guidelines June 5, 2020, regarding recommendations regarding the use of masks in the context of COVID-19, namely the use of cloth masks, medical masks, and masks. can ensure the cover of the mouth and nose, and adjust to the bridge of the nose. The result is a system with the SSDLite Mobilenet V2 model has the highest FPS compared to a system using a system with SSDMNV2. That is, the maximum FPS obtained is 3.57 FPS and the minimum FPS is 3.45 FPS

Gambaran Kepatuhan Masyarakat terhadap Protokol Keluar dan Masuk Rumah Pada Masa Pandemi Covid-19 di Kelurahan Mande Kota Bima

Coronaviruses were a large family of viruses that cause disease in humans and animals. In humans, it usually causes respiratory tract infections, ranging from the common cold to serious illnesses such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). A new type of coronavirus found in humans since an extraordinary event appeared in Wuhan, China, in December 2019, was later named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV2), and caused Coronavirus Disease-2019 (COVID-19). This research was a descriptive study to find out the description of community compliance with the protocol for leaving and entering the house during the covid-19 pandemic. This research was conducted in Mande Village, Bima City within 9 months. The population were all head of family in Mande subdistrict totaling 60 families who met the inclusion criteria. The results showed that the majority of respondents had a bachelor's level of education as many as people (71,7%). While the respondents who were the level of compliance when leaving the house were 42 people (70.3%) and when entering the home as many as 49 people (81.7%). The high level of non-compliance as many as 13 people (21.7%) was in the act of shopping using non-cash

Inflammatory reflex disruption in COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) was identified in Wuhan, China, in late 2019 and caused coronavirus disease 2019 (COVID‐19), which is still a global pandemic. In most infected people, SARS‐CoV‐2 only causes moderate symptoms, whereas in other patients, it leads to severe illness and eventually death. Although the main clinical manifestation of COVID‐19 is often seen in the lungs, this disease affects almost all body organs. The excessive and prolonged release of inflammatory cytokines that might occur in COVID‐19 patients, known as cytokine storms, stimulates undesired immune responses and can cause various tissues damage. In the current review article, we focus on the potential advantages of the intrinsic cholinergic anti‐inflammatory pathway as the efferent arm of the inflammatory reflex in COVID‐19 management. Considering this endogenous protective mechanism against chronic inflammation, we focused on the effects of SARS‐CoV‐2 in the destruction of this anti‐inflammatory system. Several studies showed the interaction of SARS‐CoV‐2 with the alpha‐7 subtype of the nicotinic acetylcholine receptor as the effector molecule of the inflammatory reflex. In contrast, neurological manifestations have increasingly been identified as significant extrapulmonary manifestations of COVID‐19. The rational connection between these findings and COVID‐19 pathogenesis might be an important issue in both our understanding of and dealing with this disease. COVID‐19 is deeply rooted in our daily life and requires an urgent need for the establishment of effective therapeutic options, and all the possible treatments must be considered for the control of such inflammatory conditions.

Identification of intrinsically disorder regions in non-structural proteins of SARS-CoV-2: New insights into drug and vaccine resistance.

The outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in December 2019 and caused coronavirus disease 2019 (COVID-19), which causes pneumonia and severe acute respiratory distress syndrome. It is a highly infectious pathogen that promptly spread. Like other beta coronaviruses, SARS‐CoV‐2 encodes some non-structural proteins (NSPs), playing crucial roles in viral transcription and replication. NSPs likely have essential roles in viral pathogenesis by manipulating many cellular processes. We performed a sequence-based analysis of NSPs to get insights into their intrinsic disorders, and their functions in viral replication were annotated and discussed in detail. Here, we provide newer insights into the structurally disordered regions of SARS-CoV-2 NSPs. Our analysis reveals that the SARS-CoV-2 proteome has a chunk of the disordered region that might be responsible for increasing its virulence. In addition, mutations in these regions are presumably responsible for drug and vaccine resistance. These findings suggested that the structurally disordered regions of SARS-CoV-2 NSPs might be invulnerable in COVID-19.

Effect of Double Mutation (L452R and E484Q) in RBD of Spike Protein on its Interaction with ACE2 Receptor Protein

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused coronavirus disease 2019 (COVID-19) pandemic has become a global health issue. Recently, the SARS-CoV-2 strain (B.1.617 double mutant variant) has raised alarms in India and other nations. B.1.617 variant was found to contain two key mutations (L452R and E484Q) in the RBD region of the spike protein. In this work, we have focussed on the effect of the double mutations in spike protein on its binding to the host cell receptor protein, angiotensin-converting enzyme 2 (ACE2). From the molecular dynamics simulation, we observed that the L452R and E484Q double mutant (DM) in spike protein utilizes unique strategies to achieve stable binding to ACE2 compared to the spike protein's wild type (WT). Using MM-GBSA/MM-PBSA algorithms, we found that the binding affinity between spike protein-containing DM and ACE2 is high (GBTOT = -47.09 kcal mol-1, PBTOT= -19.93 kcal mol-1 ) in comparison with spike protein WT and ACE2 (GBTOT =-31.79 kcal mol-1, PBTOT= -6.33 kcal mol-1). Stable binding of spike protein to ACE2 is essential for virus entry. They should understand interactions between them while designing drugs and treatment modalities to target or disrupt this interface.

Activation of TCA cycle restrains virus-metabolic hijacking and viral replication in mouse hepatitis virus-infected cells

BackgroundOne of coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused coronavirus disease 2019 (COVID-19) pandemic and threatened worldwide. However, therapy for COVID-19 has rarely been proven to possess specific efficacy. As the virus relies on host metabolism for its survival, several studies have reported metabolic intervention by SARS-CoV-2.ResultsWe investigated the coronavirus-metabolic hijacking using mouse hepatitis virus (MHV) as a surrogate for SARS-CoV-2. Based on the altered host metabolism by MHV infection, an increase of glycolysis with low mitochondrial metabolism, we tried to investigate possible therapeutic molecules which increase the TCA cycle. Endogenous metabolites and metabolic regulators were introduced to restrain viral replication by metabolic intervention. We observed that cells deprived of cellular energy nutrition with low glycolysis strongly suppress viral replication. Furthermore, viral replication was also significantly suppressed by electron transport chain inhibitors which exhaust cellular energy. Apart from glycolysis and ETC, pyruvate supplement suppressed viral replication by the TCA cycle induction. As the non-glucose metabolite, fatty acids supplement decreased viral replication via the TCA cycle. Additionally, as a highly possible therapeutic metabolite, nicotinamide riboside (NR) supplement, which activates the TCA cycle by supplying NAD+, substantially suppressed viral replication.ConclusionsThis study suggests that metabolite-mediated TCA cycle activation suppresses replication of coronavirus and suggests that NR might play a role as a novel therapeutic metabolite for coronavirus.

Tea flavonoids inhibiting multiple proteins related to SARS-CoV-2 judged from molecular docking

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused Coronavirus Disease 2019 (COVID-19) pandemic. Flavonoids-derived Chinese patent medicines have outstanding curative effects for the improvement and treatment of COVID-19. Numerous studies were suggesting that flavonoid-rich tea has antiviral effects. In vitro studies demonstrated that bioactive compounds of tea flavonoids could inhibit the activity of SARS-CoV-2 main protease (Mpro). However, bioactive compounds from tea flavonoids with antiviral effect, and the potential molecular mechanisms are unclear. In this study, we performed a molecular docking of 468 tea flavonoids and their derivatives with Mpro, RNA-dependent RNA polymerase (RdRp), angiotensin-converting enzyme 2 (ACE2), compared with the positive clinical drugs of each target. The results suggest that ACE2 and RdRp are the main targets inhibited by tea flavonoids according to the binding affinity. Quercetin 3-glycosides (Q3G), Isovitexin, and 4’,5,7-Trihydroxyflavanone 7-O-Fructoside (S)-form (TF) would be considered as the potential candidate compounds of RdRp and ACE2. Our study provides a theoretical basis for further drug design of anti-COVID-19 bioactive compounds.

Role of inflammatory and liver function markers in assessing the prognosis of patients with COVID‑19

Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) caused Coronavirus disease 2019 (COVID‑19) in early December, 2019. The disease begins as a respiratory disease with varied outcomes, from complete recovery to long‑standing complications, such as respiratory distress, heart ailments and stroke. The present study was undertaken to identify the derangements in liver function and inflammatory status which may be used to diagnose the severity and thus assess the prognosis of patients with COVID‑19 infection. The present study was conducted at a tertiary care teaching hospital. The study population included 456 patients with COVID‑19, confirmed by the reverse transcription‑PCR of nasopharyngeal swabs for SARS‑CoV‑2. Data were collected from patient files. The study was approved by the institutional ethics committee. Data are expressed based on the normality of distribution. Variables were compared and correlation analyses were performed. Receiver operating characteristics and the Youden index were applied to obtain cut‑off values. The results revealed an increase in C‑reactive protein (CRP), ferritin, D‑dimer, lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and total bilirubin levels. In addition, there was evidence of leukocytosis, neutrophilia, lymphopenia and an increased neutrophil‑to‑lymphocyte ratio (NLR). The NLR exhibited an area under the curve of 0.77, with a cut‑off value of 2.23 mg/l. Collectively, the findings of the present study demonstrate that the CRP, LDH, neutrophil and eosinophil counts along with the total leucocyte counts and absolute lymphocyte counts, NLR, erythrocyte sedimentation rate, D‑dimer, ferritin and AST levels serve to predict the severity and prognosis of patients with COVID‑19. AST appears to be a more sensitive marker than alanine aminotransferase. However, the De Ritis ratio, although not as sensitive as AST, may provide insight towards morbidity.