Viral Protein Targets Research Articles

Notes from the Field: Mpox Cluster Caused by Tecovirimat-Resistant Monkeypox Virus - Five States, October 2023-February 2024.

The antiviral drug tecovirimat* has been used extensively to treat U.S. mpox cases since the start of a global outbreak in 2022. Mutations in the mpox viral protein target (F13 or VP37) that occur during treatment can result in resistance to tecovirimat† (1,2). CDC and public health partners have conducted genetic surveillance of monkeypox virus (MPXV) for F13 mutations through sequencing and monitoring of public databases. MPXV F13 mutations associated with resistance have been reported since 2022, typically among severely immunocompromised mpox patients who required prolonged courses of tecovirimat (3-5). A majority of patients with infections caused by MPXV with resistant mutations had a history of tecovirimat treatment; however, spread of tecovirimat-resistant MPXV was reported in California during late 2022 to early 2023 among persons with no previous tecovirimat treatment (3). This report describes a second, unrelated cluster of tecovirimat-resistant MPXV among 18 persons with no previous history of tecovirimat treatment in multiple states.

Structural basis of paramyxo- and pneumovirus polymerase inhibition by non-nucleoside small-molecule antivirals.

Small-molecule antivirals can be used as chemical probes to stabilize transitory conformational stages of viral target proteins, facilitating structural analyses. Here, we evaluate allosteric pneumo- and paramyxovirus polymerase inhibitors that have the potential to serve as chemical probes and aid the structural characterization of short-lived intermediate conformations of the polymerase complex. Of multiple inhibitor classes evaluated, we discuss in-depth distinct scaffolds that were selected based on well-understood structure-activity relationships, insight into resistance profiles, biochemical characterization of the mechanism of action, and photoaffinity-based target mapping. Each class is thought to block structural rearrangements of polymerase domains albeit target sites and docking poses are distinct. This review highlights validated druggable targets in the paramyxo- and pneumovirus polymerase proteins and discusses discrete structural stages of the polymerase complexes required for bioactivity.

OASL suppresses infectious bursal disease virus replication by targeting VP2 for degrading through the autophagy pathway.

OASL (2´,5´-oligadenylate synthetase-like protein) exhibits broad-spectrum antiviral effects against single-stranded RNA viruses in mammals, potentially serving as a promising target for novel antiviral strategies. However, its role in inhibiting the replication of double-stranded RNA viruses (dsRNA viruses), such as infectious bursal disease virus (IBDV), in avian species remains unclear. Our findings indicated a unique and potent defense mechanism of OASL against dsRNA viruses. It has been previously shown in mammals that OASL inhibits virus replication through increasing interferon production. The groundbreaking aspect of our study is the finding that OASL has the ability to interact with IBDV viral protein VP2 and target it for degradation and thus exerts its antiviral effect. Our results reveal the interaction between avian natural antiviral immune response and IBDV infection. Our study not only enhances our understanding of bird defenses against viral infections but can also inform strategies for poultry disease management.

A viral movement protein targets host catalases for 26S proteasome-mediated degradation to facilitate viral infection and aphid transmission in wheat

The infection of host plants by many different viruses causes reactive oxygen species (ROS) accumulation and yellowing symptoms, but the mechanisms through which plant viruses counteract ROS-mediated immunity to facilitate infection and symptom development have not been fully elucidated. Most plant viruses are transmitted by insect vectors in the field, but the molecular mechanisms underlying virus‒host–insect interactions are unclear. In this study, we investigated the interactions among wheat, barley yellow dwarf virus (BYDV), and its aphid vector and found that the BYDV movement protein (MP) interacts with both wheat catalases (CATs) and the 26S proteasome ubiquitin receptor non-ATPase regulatory subunit 2 homolog (PSMD2) to facilitate the 26S proteasome-mediated degradation of CATs, promoting viral infection, disease symptom development, and aphid transmission. Overexpression of the BYDV MP gene in wheat enhanced the degradation of CATs, which leading to increased accumulation of ROS and thereby enhanced viral infection. Interestingly, transgenic wheat lines overexpressing BYDV MP showed significantly reduced proliferation of wingless aphids and an increased number of winged aphids. Consistent with this observation, silencing of CAT genes also enhanced viral accumulation and reduced the proliferation of wingless aphids but increased the occurrence of winged aphids. In contrast, transgenic wheat plants overexpressing TaCAT1 exhibited the opposite changes and showed increases in grain size and weight upon infection with BYDV. Biochemical assays demonstrated that BYDV MP interacts with PSMD2 and promotes 26S proteasome-mediated degradation of TaCAT1 likely in a ubiquitination-independent manner. Collectively, our study reveals a molecular mechanism by which a plant virus manipulates the ROS production system of host plants to facilitate viral infection and transmission, shedding new light on the sophisticated interactions among viruses, host plants, and insect vectors.

Repurposing of Plant-based Antiviral Molecules for the Treatment of COVID-19.

COVID-19, stemming from SARS-CoV-2, poses a formidable threat to global healthcare, with a staggering 77 million confirmed cases and 690,067 deaths recorded till December 24, 2023. Given the absence of specific drugs for this viral infection, the exploration of novel antiviral compounds becomes imperative. High-throughput technologies are actively engaged in drug discovery, and there is a parallel effort to repurpose plant-based molecules with established antiviral properties. In this context, the review meticulously delves into the potential of plant-based folk remedies and existing molecules. These substances have showcased substantial viral inhibition in diverse in vivo, in silico, and in vitro studies, particularly against critical viral protein targets, including SARS-CoV-2. The findings position these plant-based molecules as promising antiviral drug candidates for the swift advancement of treatments for COVID-19. It is noteworthy that the inherent attributes of these plant-based molecules, such as their natural origin, potency, safety, and cost-effectiveness, contribute to their appeal as lead candidates. The review advocates for further exploration through comprehensive in vivo studies conducted on animal models, emphasizing the potential of plant-based compounds to help in the ongoing quest to develop effective antivirals against COVID-19.

Inhibition of dengue viruses by N-methylcytisine thio derivatives through targeting viral envelope protein and NS2B-NS3 protease

Dengue virus (DENV) is a significant global health threat, causing millions of cases worldwide each year. Developing antiviral drugs for DENV has been a challenging endeavor. Our previous study identified anti-DENV properties of two (-)-cytisine derivatives contained substitutions within the 2-pyridone core from a pool of 19 (-)-cytisine derivatives. This study aimed to expand on the previous research by investigating the antiviral potential of N-methylcytisine thio (mCy thio) derivatives against DENV, understanding the molecular mechanisms of antiviral activity for the active thio derivatives. The inhibitory assays on DENV-2-induced cytopathic effect and infectivity revealed that mCy thio derivatives 3 ((1R,5S)-3-methyl-1,2,3,4,5,6-hexahydro-8H-1,5-methanopyrido[1,2-a][1,5]diazocine-8-thione) and 6 ((1S,5R)-3-methyl-2-thioxo-1,2,3,4,5,6-hexahydro-8H-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one) were identified as the active compounds against both DENV-1 and DENV-2. Derivative 6 displayed robust antiviral activity against DENV-2, with EC50 values ranging from 0.002 to 0.005 μM in different cell lines. Derivative 3 also exhibited significant antiviral activity against DENV-2. The study found that these compounds are effective at inhibiting DENV-2 at both the entry stage (including virus attachment) and post-entry stages of the viral life cycle. The study also investigated the inhibition of the DENV-2 NS2B-NS3 protease activity by these compounds. Derivative 6 demonstrated notably stronger inhibition compared to mCy thio 3, revealing its dual antiviral action at both the entry and post-entry stages. Molecular docking simulations indicated that mCy thio derivatives 3 and 6 bind to the domain I and III of the DENV E protein, as well as the active of NS2B-NS3 protease, suggesting their molecular interactions with the virus. The study demonstrates the antiviral efficacy of N-methylcytisine thio derivatives against DENV. It provides valuable insights into the potential interactions between these compounds and viral target proteins, which could be useful in the development of antiviral drugs for DENV.

Synthesis of 5-heptadecyl-4H-1,2,4-triazole incorporated indole moiety: Antiviral (SARS-CoV-2), antimicrobial, and molecular docking studies

Two series of Schiff bases and Mannich bases derived from 5-heptadecyl-4H-1,2,4-triazole hybrids of indole moiety have been synthesized. First, the acid-catalyzed reaction of N-substituted-1H-indole-3-carboxaldehydes with the modified fatty acid, 4-amino-5-heptadecyl-4H-1,2,4-triazole-3-thiol, afforded 1,2,4-triazole Schiff bases 5a-d. Treatment of 5a-d with some halo-compounds gave S-alkyl-1,2,4-triazoles 6a-d to 9a-d. Additionally, the reaction of 5a-d with different secondary amine and paraformaldehyde afforded Mannich base products 10a-d to 13a-d. Basically, viral infections are often followed by bacterial infections that require antimicrobial treatment. The antiviral bioassay revealed that compounds 6d and 7d exhibited significant antiviral activity against NRC-03-nhCoV with IC50 equal 8.7 and 8.925 μM, respectively. Next, the synthesized compounds were evaluated for their antimicrobial activity against Gram-positive and Gram-negative bacteria as well as yeast and fungi. Compound 5b exhibited effective antimicrobial activities against all microbial test strains. 5b revealed MIC values of 19.53 μg/mL against S. aureus, 39.063 μg/mL against E. coli, and 39.125 μg/mL against C. albicans. On top of that, the release of reducing sugars and proteins from the treated bacterial strains over the untreated bacterial strains was undertaken to describe the effect of compound 5b on the intact cells. Furthermore, scanning electron microscopy (SEM) has been applied to study the possible sterilization process of the antimicrobial compound 5b. The results indicated the possibility of destroying the cell membrane structure of microbes, resulting in incomplete microbial structures, and thus achieving inhibition. To putatively highlight the antiviral and antimicrobial activities of the potent compounds, they were subjected to molecular docking against the key viral and microbial protein targets.

Cell Fractionation and the Identification of Host Proteins Involved in Plant-Virus Interactions.

Plant viruses depend on host cellular factors for their replication and movement. There are cellular proteins that change their localization and/or expression and have a proviral role or antiviral activity and interact with or target viral proteins. Identification of those proteins and their roles during infection is crucial for understanding plant-virus interactions and to design antiviral resistance in crops. Important host proteins have been identified using approaches such as tag-dependent immunoprecipitation or yeast two hybridization that require cloning individual proteins or the entire virus. However, the number of possible interactions between host and viral proteins is immense. Therefore, an alternative method is needed for proteome-wide identification of host proteins involved in host-virus interactions. Here, we present cell fractionation coupled with mass spectrometry as an option to identify protein-protein interactions between viruses and their hosts. This approach involves separating subcellular organelles using differential and/or gradient centrifugation from virus-free and virus-infected cells (1) followed by comparative analysis of the proteomic profiles obtained for each subcellular organelle via mass spectrometry (2). After biological validation, prospect host proteins with proviral or antiviral roles can be subject to fundamental studies in the context of basic biology to shed light on both virus replication and cellular processes. They can also be targeted via gene editing to develop virus-resistant crops.

Systematic discovery of virus-perturbed molecular pathways linking to schizophrenia

<p><b>V</b>irus infections increase risk of psychiatric disorders. Immune activation-mediated perturbation of cellular function is currently proposed as a potential mechanism. Here, we report an alternative mechanism: viral protein-mediated perturbation of molecular pathways. We collected high-quality interactions between human proteins and proteins of neurotrophic viruses, and found that viral targets were enriched with candidate genes of psychiatric disorders, such as schizophrenia (SCZ) and autism spectrum disorder. The viral targets were further mapped onto a high-quality protein interaction network for SCZ (the SCZ Network), and the viral proteins tend to bind hub proteins in the network, suggesting that viral proteins may perturb molecular pathways involved in SCZ. Both immune genes and non-immune genes in this network are likely to be targets of viral proteins, suggesting that the viral infection may lead to SCZ via perturbing immune and nonimmune functions. Using pull-downs coupled with mass spectrometry, 96 human proteins were identified to interact with HIV-1 Vpr. These HIV-1 Vpr targets are enriched with proteins encoded by SCZ candidate genes. AAVs carrying HIV-1 Vpr were stereotactically injected into the prefrontal cortex of mice, and the mice with HIV-1 Vpr expression displayed impairments in object recognition and enhanced anxiety. These results suggest that viruses infecting the brain cells may interfere with cellular functions of the brain through interactions between viral proteins and host proteins.</p>

Artificial intelligence-aiding lab-on-a-chip workforce designed oral [3.1.0] bi and [4.2.0] tricyclic catalytic interceptors inhibiting multiple SARS-CoV-2 protomers assisted by double-shell deep learning.

While each massive pandemic has claimed the lives of millions of vulnerable populations over the centuries, one limitation exists: that the Edisonian approach (human-directed with trial errors) relies on repurposing pharmaceuticals, designing drugs, and herbal remedies with the violation of Lipinski's rule of five druglikeness. It may lead to adverse health effects with long-term health multimorbidity. Nevertheless, declining birth rates and aging populations will likely cause a shift in society due to a shortage of a scientific workforce to defend against the next pandemic incursion. The challenge of combating the ongoing post-COVID-19 pandemic has been exacerbated by the lack of gold standard drugs to deactivate multiple SARS-CoV-2 protein targets. Meanwhile, there are three FDA-approved antivirals, Remdesivir, Molnupiravir, and Paxlovid, with moderate clinical efficacy and drug resistance. There is a pressing need for additional antivirals and prepared omics technology to combat the current and future devastating coronavirus pandemics. While there is a limitation of existing contemporary inhibitors to deactivate viral RNA replication with minimal rotational bonds, one strategy is to create Lipinski inhibitors with less than 10 rotational bonds and precise halogen bond placement to destabilize multiple viral protomers. This work describes the efforts to design gold-standard oral inhibitors of bi- and tri-cyclic catalytic interceptors with electrophilic heads using double-shell deep learning. Here, KS1 with and KS2 compounds designed by lab-on-a-chip technology attain 5-fold novel filtered-Lipinski, GHOSE, VEBER, EGAN, and MUEGGE druglikeness. The graph neural network (GNN) relies on module-initiation, expansion, relabeling atom index, and termination (METORITE) iterations, while the deep neural network (DNN) engages pinning, extraction, convolution, pooling, and flattening (PROOF) operations. The cyclic compound's specific halogen atom location enhances the nitrile catalytic head, which deactivates several viral protein targets. Initiating this lab-on-a-chip that is not susceptible to the aging process for creating clinical compounds can leverage a new path to many valuable drugs with speedy oral drug discovery, especially to defend the loss of vulnerable population and prevent multimorbidity that is susceptible to hidden viral persistence in the continuing aging times.

25 Years Responding to Respiratory and Other Viruses with Mass Spectrometry.

This review article presents the development and application of mass spectrometry (MS) approaches, developed in the author's laboratory over the past 25 years, to detect; characterise, type and subtype; and distinguish major variants and subvariants of respiratory viruses such as influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). All features make use of matrix-assisted laser desorption ionisation (MALDI) mass maps, recorded for individual viral proteins or whole virus digests. A MALDI-based immunoassay in which antibody-peptide complexes were preserved on conventional MALDI targets without their immobilisation led to an approach that enabled their indirect detection. The site of binding, and thus the molecular antigenicity of viruses, could be determined. The same approach was employed to study antivirals bound to their target viral protein, the nature of the binding residues, and relative binding affinities. The benefits of high-resolution MS were exploited to detect sequence-conserved signature peptides of unique mass within whole virus and single protein digests. These enabled viruses to be typed, subtyped, their lineage determined, and variants and subvariants to be distinguished. Their detection using selected ion monitoring improved analytical sensitivity limits to aid the identification of viruses in clinical specimens. The same high-resolution mass map data, for a wide range of viral strains, were input into a purpose-built algorithm (MassTree) in order to both chart and interrogate viral evolution. Without the need for gene or protein sequences, or any sequence alignment, this phylonumerics approach also determines and displays single-point mutations associated with viral protein evolution in a single-tree building step.

An integrated strategy combining UPLC-MS/MS, chemometrics, molecular docking, and molecular dynamics simulation for metabolic profiling of onion (Allium cepa L.) cultivars and unravelling potential anti-COVID-19 metabolites

Onion has been historically valued for its various health promoting activities. It has been traditionally used to treat various infectious diseases and alleviate the symptoms of several respiratory ailments. However, the therapeutic potential of the plant against respiratory viruses remains meager. This study aimed to investigate the metabolic profiles of bulb extracts of four onion cultivars (red, copper-yellow, golden yellow and white onions) using UPLC-MS/MS combined to chemometrics. Further, the extracts were assessed for their potential anti-COVID-19 activity against the omicron sub-variant BA.5 of SARS-CoV-2. A total of 81 metabolites of diverse chemical classes were identified including amino acids and peptides, flavonoids, phenolic acids, saponins and fatty acids. The four cultivars displayed significant variations in their chemical composition, with copper-yellow onion exhibiting the richest metabolic profile which distinguished it from the others. Except for white onion, the tested cultivars displayed promising anti-COVID-19 activities (IC50 9.78–16.39 μg/mL) and effectively downregulated viral RNA dependent RNA polymerase (RdRp) and envelope (E) genes. Multivariate analysis revealed potential anti-COVID-19 bioactive metabolites. Among them, chlorogenic, caffeic acids, and kaempferol effectively inhibited viral RdRp and E genes in vitro, with a % downregulation of (86 %, 79 %), (80 %, 73 %), and (82 %, 70 %), respectively, at 30 μg/mL. The results from in vitro testing were corroborated by molecular docking and dynamics studies as the compounds showed significant interactions with the viral target proteins forming stable protein-ligand complexes. This study increments the value of metabolomics as a promising tool for cultivar differentiation. Conjointly, it lays the groundwork for future research into the anti-COVID-19 potential of onion as a valuable source of bioactive compounds.

A viral protein targets mitochondria and chloroplasts by subverting general import pathways and specific receptors.

Many plant proteins and some proteins from plant pathogens are dually targeted to chloroplasts and mitochondria, and are supposed to be transported along the general pathways for organellar protein import, but this issue has not been explored yet. Moreover, organellar translocon receptors exist as families of several members whose functional specialization in different cargos is supposed but not thoroughly studied. This article provides novel insights into such topics showing for the first time that an exogenous protein, the melon necrotic spot virus coat protein, exploits the common Toc/Tom import systems to enter both mitochondria and chloroplasts while identifying the involved specific receptors.

Antiviral Drug Target Identification and Ligand Discovery.

This chapter intends to provide a general overview of web-based resources available for antiviral drug discovery studies. First, we explain how the structure for a potential viral protein target can be obtained and then highlight some of the main considerations in preparing for the application of receptor-based molecular docking techniques. Thereafter, we discuss the resources to search for potential drug candidates (ligands) against this target protein receptor, how to screen them, and preparing their analogue library. We make specific reference to free, online, open-source tools and resources which can be applied for antiviral drug discovery studies.

Small Molecules Targeting Viral RNA.

The majority of antivirals available target viral proteins; however, RNA is emerging as a new and promising antiviral target due to the presence of highly structured RNA in viral genomes fundamental for their replication cycle. Here, we discuss methods for the identification of RNA-targeting compounds, starting from the determination of RNA structures either from purified RNA or in living cells, followed by in silico screening on RNA and phenotypic assays to evaluate viral inhibition. Moreover, we review the small molecules known to target the programmed ribosomal frameshifting element of SARS-CoV-2, the internal ribosomal entry site of different viruses, and RNA elements of HIV.

Broad-Spectrum, Potent, and Durable Ceria Nanoparticles Inactivate RNA Virus Infectivity by Targeting Virion Surfaces and Disrupting Virus-Receptor Interactions.

There is intense interest in developing long-lasting, potent, and broad-spectrum antiviral disinfectants. Ceria nanoparticles (CNPs) can undergo surface redox reactions (Ce3+ ↔ Ce4+) to generate ROS without requiring an external driving force. Here, we tested the mechanism behind our prior finding of potent inactivation of enveloped and non-enveloped RNA viruses by silver-modified CNPs, AgCNP1 and AgCNP2. Treatment of human respiratory viruses, coronavirus OC43 and parainfluenza virus type 5 (PIV5) with AgCNP1 and 2, respectively, prevented virus interactions with host cell receptors and resulted in virion aggregation. Rhinovirus 14 (RV14) mutants were selected to be resistant to inactivation by AgCNP2. Sequence analysis of the resistant virus genomes predicted two amino acid changes in surface-located residues D91V and F177L within capsid protein VP1. Consistent with the regenerative properties of CNPs, surface-applied AgCNP1 and 2 inactivated a wide range of structurally diverse viruses, including enveloped (OC43, SARS-CoV-2, and PIV5) and non-enveloped RNA viruses (RV14 and feline calicivirus; FCV). Remarkably, a single application of AgCNP1 and 2 potently inactivated up to four sequential rounds of virus challenge. Our results show broad-spectrum and long-lasting anti-viral activity of AgCNP nanoparticles, due to targeting of viral surface proteins to disrupt interactions with cellular receptors.

Herbal Therapeutics as Potential Prophylaxis for SARS-CoV-2 Infection

Introduction: The global pandemic COVID-19 and its uncontrolled spread and lack of effective therapeutics demand to investigate the herbal resources in search of novel, safe and potent therapeutics. Herbal medicines have proven the advantage of multi-target potential and thus can be investigated for virus-host interaction protein and viral protein targets. Objectives: Manuscript aims to provide an outcome-based analysis of studies performed towards evaluation of herbal compounds as anti-COVID agents. The studies focus on the proposed mechanism of viral inhibition by herbal compounds. Methods: The details on modern drug discovery approaches for investigation of potential antiviral agents includes in silico screening, ADMET and molecular docking studies. It helps to establish the probable mechanism of viral inhibition as well as to establish pharmacophore. The reports explaining role of herbal therapeutics/phytochemicals in antiviral drug development have been thoroughly searched. Results: The study summarizes herbal therapeutics and phytochemicals based on their antiviral properties against various pathogenic viruses. Herbal compounds that have an interesting role in the development of therapeutics and herd immunity against SARS-CoV-2 are included and discussed. Conclusion: The manuscript provides a summarized description of herbal resources and phytochemicals which are under investigation or have been investigated as potential therapeutic option for SARS-COV-2 inhibition. It will be a useful resource for researchers interested in the development of herbal therapeutics for the prevention and/or treatment of COVID-19.

In silico identification and validation of phenolic lipids as potential inhibitor against bacterial and viral strains

The recurrence of coronavirus disease and bacterial resistant strains has drawn attention to naturally occurring bioactive molecules that can demonstrate broad-spectrum efficacy against bacteria as well as viral strains. The drug-like abilities of naturally available “anacardic acids” (AA) and their derivatives against different bacterial and viral protein targets through in-silico tools were explored. Three viral protein targets [P DB: 6Y2E (SARS-CoV-2), 1AT3 (Herpes) and 2VSM (Nipah)] and four bacterial protein targets [P DB: 2VF5 (Escherichia coli), 2VEG (Streptococcus pneumoniae), 1JIJ (Staphylococcus aureus) and 1KZN (E. coli)] were selected to evaluate the activity of bioactive AA molecules. The potential ability to inhibit the progression of microbes has been discussed based on the structure, functionality and interaction ability of these molecules on the selected protein targets for multi-disease remediation. The number of interactions, full-fitness value and energy of the ligand-target system were determined from the docked structure in SwissDock and Autodock Vina. In order to compare the efficacy of these active derivatives to that of commonly used drugs against bacteria and viruses, a few of the selected molecules were subjected to 100 ns long MD simulations. It was found that the phenolic groups and alkyl chains of AA derivatives are more likely to bind with microbial targets, that could be responsible for the improved activity against these targets. The results suggest that the proposed AA derivatives have demonstrated potential to become active drug ingredients against microbial protein targets. Further, experimental investigations are essential for clinical verification of the drug-like abilities of AA derivatives. Communicated by Ramaswamy H. Sarma

A computationally designed ACE2 decoy has broad efficacy against SARS-CoV-2 omicron variants and related viruses in vitro and in vivo

SARS-CoV-2, especially B.1.1.529/omicron and its sublineages, continues to mutate to evade monoclonal antibodies and antibodies elicited by vaccination. Affinity-enhanced soluble ACE2 (sACE2) is an alternative strategy that works by binding the SARS-CoV-2 S protein, acting as a ‘decoy’ to block the interaction between the S and human ACE2. Using a computational design strategy, we designed an affinity-enhanced ACE2 decoy, FLIF, that exhibited tight binding to SARS-CoV-2 delta and omicron variants. Our computationally calculated absolute binding free energies (ABFE) between sACE2:SARS-CoV-2 S proteins and their variants showed excellent agreement to binding experiments. FLIF displayed robust therapeutic utility against a broad range of SARS-CoV-2 variants and sarbecoviruses, and neutralized omicron BA.5 in vitro and in vivo. Furthermore, we directly compared the in vivo therapeutic efficacy of wild-type ACE2 (non-affinity enhanced ACE2) against FLIF. A few wild-type sACE2 decoys have shown to be effective against early circulating variants such as Wuhan in vivo. Our data suggest that moving forward, affinity-enhanced ACE2 decoys like FLIF may be required to combat evolving SARS-CoV-2 variants. The approach described herein emphasizes how computational methods have become sufficiently accurate for the design of therapeutics against viral protein targets. Affinity-enhanced ACE2 decoys remain highly effective at neutralizing omicron subvariants.

Machine Learning Approach to Identify Receptor Binding Domain of Spike Glycoprotein as A Potential Vaccine Candidate for COVID-19

Recent SARS-CoV-2 outbreaks have spurred continuing efforts to exploit different viral protein targets for therapy, but preventing viral proteins, including in therapeutic and vaccine research, has largely failed. In the lack of clear clinical proof for COVID-19 pathogenesis, a comparison of previous pandemic HCoVs-related immune system reactions could provide insight into COVID-19 pathogenesis. Authors summarize the possible genesis and method of spread of COVID-19, in addition to our present understanding of the viral genome integrity of known outbreak viruses against SARS-CoV-2 in this study. The COVID-19 pandemic continues to be a major concern for health-care systems globally. Accurate and timely identification of SARS Coronavirus 2 (SARS-CoV-2) infection is crucial for limiting dissemination and commencing therapy. The gold standard among test procedures is real-time reverse-transcriptase polymerase-chain reaction (rRT-PCR). Despite the fact that this test has a high specificity and sensitivity, the incidence of erroneously negative findings in patients with symptoms and/or having a positive CT scan remains a difficulty. In this article authors analyze the receptor binding domain of spike glycoprotein to be potential vaccine candidates.