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Article
Multidisciplinary Sciences
Sho Iketani et al.
Summary: Nirmatrelvir, an experimental oral antiviral, has shown clinical usefulness against COVID-19. However, there is concern that SARS-CoV-2 could develop resistance to this drug. In vitro studies have demonstrated that highly resistant viruses can emerge from SARS-CoV-2 when exposed to Nirmatrelvir, with mutations in the 3CL protease. These findings provide insights into the mechanisms of resistance and can inform the development of next-generation protease inhibitors.
Review
Biochemistry & Molecular Biology
Anoop Narayanan et al.
Summary: This article provides an overview of the structures and functions of two proteases, 3CLpro and PLpro, encoded by the SARS-CoV-2 coronavirus. It examines the strategies of structure-based drug designing and drug repurposing against these proteases. Several protease inhibitors have been identified, and some candidates are undergoing trials that may prove to be effective antivirals against SARS-CoV-2.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2022)
Review
Infectious Diseases
Mostafa Akbarzadeh-Khiavi et al.
Summary: The combination therapy of Janus kinase (JAK) inhibitor baricitinib has shown positive therapeutic outcomes in hospitalized COVID-19 patients, by modulating the inflammatory response and controlling cytokine storm induction. This strategy may be a potential treatment option for severe cases of COVID-19 with the standard of care.
Article
Chemistry, Medicinal
Zhengnan Shen et al.
Summary: Researchers have discovered a new antiviral drug that targets the SARS-CoV-2 papain-like protease (PLpro) to inhibit viral replication and improve antiviral potency in human cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Eric W. Sayers et al.
Summary: The National Center for Biotechnology Information (NCBI) produces a variety of online information resources for biology, including databases for nucleic acid sequences and life science journal citations. It provides search and retrieval operations for most of these data from 35 distinct databases, with E-utilities serving as the programming interface. Several resources received significant updates in the past year.
NUCLEIC ACIDS RESEARCH
(2022)
Letter
Cell Biology
Yao Zhao et al.
Review
Chemistry, Multidisciplinary
Zongyang Lv et al.
Summary: The emergence of SARS-CoV-2 has led to the search for new antiviral drugs. The papain-like protease and main protease have been identified as potential drug targets. Promising drug candidates have been discovered that show inhibitory effects against these proteases, encouraging further research and optimization.
FRONTIERS IN CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Sven Ullrich et al.
Summary: The COVID-19 pandemic continues to pose a threat to public health, with emerging variants of SARS-CoV-2 potentially impacting the effectiveness of available vaccines. However, research suggests that the specific M-pro inhibitor nirmatrelvir remains effective against these variants.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Review
Biochemistry & Molecular Biology
Janos Andras Motyan et al.
Summary: COVID-19 is a devastating pandemic caused by SARS-CoV-2. The lack of effective antiviral drugs has led to global health crises. Pfizer's newly approved nirmatrelvir has shown promise as an inhibitor of the viral main protease, offering hope for both therapeutic and prophylactic use against the infection. However, the high mutation rates of RNA viruses highlight the importance of considering lessons learned from previous pandemics to avoid the emergence of resistance mutations in long-term use of novel inhibitors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Laura J. Stevens et al.
Summary: This study identified mutations in the nonstructural protein 12 RNA-dependent RNA polymerase of the SARS-CoV-2 virus that confer resistance to the antiviral drug remdesivir. These mutations result in decreased preference for the drug as a substrate and can be transferred to other betacoronaviruses, causing replication defects and up to 38-fold resistance. The findings highlight the importance of further research to understand and prevent the emergence of remdesivir resistance mutations in clinical settings.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Shiv Gandhi et al.
Summary: This article reports a case of remdesivir resistance mutation in an immunocompromised patient with SARS-CoV-2 infection. The patient developed viral shedding recurrence and whole genome sequencing identified a mutation, E802D, in the nsp12 RNA-dependent RNA polymerase. In vitro experiments showed that this mutation increased remdesivir resistance but had a fitness cost in the absence of remdesivir. The patient achieved sustained clinical and virologic response with casirivimab-imdevimab treatment.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Karine Mazmanian et al.
Summary: This study investigates the reactivity of cysteine in proteins using combined quantum mechanical/continuum calculations and identifies novel targets for combating SARS-CoV-2. The researchers propose a multi-targeting strategy that enhances antiviral effects and prevents drug resistance by targeting multiple conserved viral proteins using a Zn-ejector drug.
WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Weizhu Yan et al.
Summary: SARS-CoV-2 is the causative agent of COVID-19 and understanding the structures of its proteins and potential therapy agents is crucial for prevention and treatment of viral infections.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Review
Chemistry, Multidisciplinary
Hailei Su et al.
Summary: This article summarizes and analyzes recent studies on the molecular mechanisms of promising antiviral drugs for COVID-19, focusing on viral targets such as spike glycoprotein and host proteases, aiming to inspire new ideas for drug design and optimization in the future.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Multidisciplinary Sciences
Tyler N. Starr et al.
Summary: Research has found that mutations in the receptor binding domain (RBD) of SARS-CoV-2 may potentially escape the action of the REGN-COV2 cocktail, providing important information for interpreting mutations observed during viral surveillance.
Article
Multidisciplinary Sciences
Ziyang Fu et al.
Summary: SARS-CoV-2 PLpro enzyme plays a critical role in virus maturation, host inflammation regulation, and antiviral immune responses, making it a promising drug target. The inhibitor GRL0617 has shown to effectively inhibit PLpro and has promising antiviral activity in vitro. This study provides insights into the mechanism of action of GRL0617 and highlights the potential of targeting the PLpro enzyme for antiviral drug discovery.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Ridhima Kaul et al.
Summary: This review summarizes the activities and structure-activity relationships of flavonoids in combating SARS-CoV-2 from in vitro studies to clinical research. The study found that flavonoids such as quercetin and myricetin derivatives, baicalein, baicalin, EGCG, and tannic acid show promising activities against SARS-CoV-2.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Physical
Amgad M. Rabie
Summary: Polyhydroxyphenols and nitrogenous heterocyclics are potent active species in pharmaceutical chemistry with antiviral activities. Computational screening revealed Taroxaz-104 as a potential compound with inhibitory effects against SARS-CoV-2, specifically targeting the RNA-dependent RNA polymerase enzyme. Further research and trials are needed for its development as an anti-SARS-CoV-2 medication.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Review
Biotechnology & Applied Microbiology
Molly K. Roe et al.
Summary: Coronavirus protease nsp5 (M-pro, 3CL(pro)) is a key target for coronavirus therapeutics due to its crucial role in the proteolytic processing of viral replicase polyproteins. This review discusses the structure, function, and efforts to develop inhibitors targeting nsp5, providing potential innovative strategies for effective therapeutics against the coronavirus protease.
JOURNAL OF GENERAL VIROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Wanchao Yin et al.
Summary: Suramin, an old drug, serves as a potent inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase by blocking RNA binding. It is at least 20 times more effective than the approved nucleotide drug for COVID-19 treatment, remdesivir. The cryo-electron microscopy structure of the viral RdRp complexed with suramin reveals its mechanism of action in inhibiting viral replication.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Jerzy Osipiuk et al.
Summary: The study focused on papain-like protease (PLpro) as a potential target for antivirals against SARS-CoV-2, identifying inhibitors and their interactions with the enzyme. The findings demonstrate the potential for developing high-affinity inhibitors through structure-based drug design efforts targeting PLpro.
NATURE COMMUNICATIONS
(2021)
Review
Chemistry, Multidisciplinary
Hylemariam Mihiretie Mengist et al.
Summary: The COVID-19 pandemic continues to devastate the world without approved antiviral drugs or vaccines, leading to rising cases and deaths. Current patient management relies on supportive care and repurposed drugs, while ongoing studies focus on potential inhibitors to the main protease of SARS-CoV-2.
FRONTIERS IN CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Ross Martin et al.
Summary: The study reveals low genetic variation in the RNA replication complex of SARS-CoV-2, especially the RNA-dependent RNA polymerase (nsp12), which is the main target of remdesivir. The risk of pre-existing resistance to remdesivir is minimal.
ANTIVIRAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Navaneethakrishnan Krishnamoorthy et al.
Summary: A study identified 24 mutational coldspots in the SARS-CoV2 main protease (M-pro), with three coldspot residues assisting in forming the active site and seven contributing to dimer formation necessary for M-pro activity. The surface of the dimer interface is more resistant to mutations compared to the active site, and most coldspots are found in conserved clusters across coronaviruses. Identification of these coldspots provides a new perspective for targeting SARS-CoV2 M-pro while avoiding mutation-based drug resistance.
Article
Virology
Raphael J. Eberle et al.
Summary: The study found that quinacrine and suramin have inhibitory effects on the SARS-CoV-2 main protease, and their combined use can enhance the inhibitory effect. Experimental results showed that quinacrine and suramin exhibited competitive and noncompetitive inhibition modes, respectively, suggesting a new approach for the treatment of COVID-19.
Article
Cell Biology
Yao Zhao et al.
Summary: This study identified four compounds that inhibit SARS-CoV-2 PLpro with strong antiviral activities, particularly highlighting YM155's unique binding mode targeted at three hot spots on PLpro, suggesting their potential as clinical leads for COVID-19 treatments.
Article
Pharmacology & Pharmacy
Ruikun Du et al.
Summary: The study found that chebulagic acid and punicalagin can inhibit the replication of SARS-CoV-2 virus in cells, and reduce virus-induced plaque formation at noncytotoxic concentrations, by regulating the enzymatic activity of viral protease as allosteric regulators.
ANTIVIRAL RESEARCH
(2021)
Article
Chemistry, Medicinal
Samia A. Elseginy et al.
Summary: The study aimed to develop novel antiviral compounds with dual activity against SARS-CoV-2 by targeting valuable less-mutated enzymes. Experimental results showed that compounds 7 and 13 exhibited significant inhibitory activity against different proteases, potential resistance to SARS-CoV-2, and no toxicity on mammalian cells.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemical Research Methods
Setayesh Yazdani et al.
Summary: The strategy of targeting highly conserved binding sites on SARS-CoV-2 proteins can lead to the development of drugs that work against multiple coronaviruses; the two most conserved binding sites are the RNA binding site of the helicase nsp13 and the catalytic site of the RNA-dependent RNA polymerase nsp12.
JOURNAL OF PROTEOME RESEARCH
(2021)
Review
Microbiology
William T. Harvey et al.
Summary: The evolution of SARS-CoV-2 has been characterized by the emergence of mutations and variants that impact virus characteristics. Manufacturers are preparing for possible updates to vaccines in response to changes in the virus population, and it is crucial to monitor genetic and antigenic changes alongside experiments to understand the impacts of mutations.
NATURE REVIEWS MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Florian Kabinger et al.
Summary: Molnupiravir is an oral antiviral drug candidate that increases viral RNA mutations frequency and inhibits replication of SARS-CoV-2 by altering the substrate preference of RdRp. This two-step mutagenesis mechanism can explain the broad-spectrum antiviral activity of molnupiravir, making it a promising COVID-19 treatment option.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Kangsa Amporndanai et al.
Summary: The study demonstrates that ebselen and its derivatives can effectively inhibit the SARS-CoV-2 main protease with potent antiviral activity. Further analysis reveals that the derivatives show stronger inhibition and ability to rescue infected cells compared to ebselen. The crystallographic structures also confirm the formation of enzyme-bound organoselenium covalent adducts through hydrolysis mechanism, suggesting broader therapeutic applications against SARS-CoV-2 and other zoonotic beta-corona viruses.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Stephanie Patchett et al.
Summary: The study identified the S1 sensor region within the SARS-CoV-2 papain-like protease as a key determinant of substrate specificity. Variations in this region specifically alter cleavage of different substrates, which could potentially impact host antiviral immune responses to newly emerging SARS-CoV-2 lineages.
Article
Microbiology
Agnieszka M. Szemiel et al.
Summary: This study selected drug-resistant SARS-CoV-2 populations with decreased sensitivity to remdesivir (RDV) in vitro, identifying a mutation in NSP12 that decreases RDV sensitivity. There is no evidence of widespread transmission of RDV-resistant mutants among globally circulating SARS-CoV-2 variants. Additionally, emerging SARS-CoV-2 variants showed substitutions at Spike sites corresponding to those identified in vitro, indicating their potential to arise without immune selection.
Article
Virology
David VanInsberghe et al.
Article
Multidisciplinary Sciences
Simon Pollett et al.
Summary: The study evaluated recombination in the evolution of human coronaviruses, finding evidence of recombination events in SARS-CoV-2, SARS-CoV-1, and other coronaviruses. Recombination breakpoints were more likely to occur in the non-ORF1 region of the genome containing structural genes, significantly affecting the temporal structure of the data. The findings underscore the importance of genomic surveillance to detect recombination, especially in SARS-CoV-2, which could potentially lead to immune evasion.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Medicinal
Ting Chen et al.
Summary: This study targets multiple conserved domains of the SARS-CoV-2 replication and transcription complex (RTC) using clinically safe Zn-ejector drugs disulfiram and ebselen to inhibit key activities of nsp13 and nsp14, showing a synergistic inhibition of viral replication when combined with remdesivir.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2021)
Article
Immunology
Thiago Carvalho et al.
Summary: The timeline of major scientific discoveries during the first year of the COVID-19 pandemic highlights the collaborative efforts that led to rapid progress in understanding the immune response to SARS-CoV-2. It showcases the unprecedented convergence of research efforts on COVID-19 and identifies gaps in knowledge for future investigations.
NATURE REVIEWS IMMUNOLOGY
(2021)
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NUCLEIC ACIDS RESEARCH
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MOLECULAR BIOLOGY AND EVOLUTION
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MOLECULAR BIOLOGY AND EVOLUTION
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N Barretto et al.
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(2005)
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SLK Pond et al.
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