Resources and computational strategies to advance small molecule SARS-CoV-2 discovery: Lessons from the pandemic and preparing for future health crises

Singh, Natesh; Villoutreix, Bruno O.

doi:10.1016/j.csbj.2021.04.059

Cited by 20 publications

(14 citation statements)

References 271 publications

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“…The SARS-CoV-2 infiltrates human cells through an interaction between the virus S1 spike protein and the ACE2 receptor, a mechanism that has been extensively studied and characterized using various structural [38] , [39] and computational [40] , [41] , [42] , [43] , [44] techniques. Therefore, we felt it was useful to employ our computational setup to find relevant binding poses and dynamical features of the spike protein-ACE2 complexes and benchmark the obtained results with relevant literature data.…”

Section: Resultsmentioning

confidence: 99%

COVID-19 infection and neurodegeneration: Computational evidence for interactions between the SARS-CoV-2 spike protein and monoamine oxidase enzymes

Hok

Rimac

Mavri

et al. 2022

Computational and Structural Biotechnology Journal

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Section: Resultsmentioning

confidence: 99%

COVID-19 infection and neurodegeneration: Computational evidence for interactions between the SARS-CoV-2 spike protein and monoamine oxidase enzymes

Hok

Rimac

Mavri

et al. 2022

Computational and Structural Biotechnology Journal

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“…In general, there are several computational strategies, including structure-based and deep-learning-based methods targeting virus, and signature-based and network-based approaches targeting host. 74 Our approach relied on a signature-based host-targeting method to identify potential drugs that can induce expression signatures that reversely correlate with the disease development and progression by altering the host immune response against viral pathogenesis. 45 Our approach is different from previous methods 41–44 for drug repurposing for coronavirus as it does not merely rapidly identify likely effective therapeutic agents in preventing or treating COVID-19, but tries to filter specific medications targeting immune reactions and specific modulators during the patients’ disease courses.…”

Section: Discussionmentioning

confidence: 99%

Repurposable drugs for SARS-CoV-2 and influenza sepsis with scRNA-seq data targeting post-transcription modifications

Wang

Guo

Gao

et al. 2021

Precision Clinical Medicine

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Coronavirus disease 2019 (COVID-19) has been impacting almost every part of human life worldwide, posing a massive threat to human health. Due to the lack of time for new drug discovery and the urgent need for rapid disease control, drug repurposing presents a quick and effective alternative to finding therapeutics to reduce mortality. To identify potentially repurposable drugs, we employed a systematic approach to mine candidates from U.S. FDA-approved drugs and preclinical small-molecule compounds by integrating the gene expression perturbation data for chemicals from the Library of Integrated Network-Based Cellular Signatures project with a publicly available single-cell RNA sequencing dataset from mild and severe COVID-19 patients (GEO: GSE145926, public data available and accessed on April 22, 2020). We identified 281 FDA-approved drugs that have the potential to be effective against SARS-CoV-2 infection, 16 of which are currently undergoing clinical trials to evaluate their efficacy against COVID-19. We experimentally tested and demonstrated the inhibitory effects of tyrphostin-AG-1478 and brefeldin-a, two chemical inhibitors of glycosylation (a post-translational modification) on the replication of the single-stranded ribonucleic acid (ssRNA) virus influenza A virus as well as on the transcription and translation of host cell cytokines and their regulators (IFNs and ISGs). In conclusion, we have identified and experimentally validated repurposable anti-SARS-CoV-2 and IAV drugs using a systems biology approach, which may have the potential for treating these viral infections and their complications (sepsis).

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“…Several researchers tried to identify the repurposed drugs for COVID-19 through this process. Therefore, computational drug repurposing is a prominent area for the pandemic period of COVID-19 ( Galindez et al, 2021 ; Luo et al, 2021 ; Singh and Villoutreix, 2021 ; Srivastava and Singh, 2021 ).…”

Section: Lessons Learned From Computational Drug Repurposing For Covid-19: Another Effort For Drug Discovery Of Covid-19mentioning

confidence: 99%

The Drug Repurposing for COVID-19 Clinical Trials Provide Very Effective Therapeutic Combinations: Lessons Learned From Major Clinical Studies

et al. 2021

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SARS-CoV-2 has spread across the globe in no time. In the beginning, people suffered due to the absence of efficacious drugs required to treat severely ill patients. Nevertheless, still, there are no established therapeutic molecules against the SARS-CoV-2. Therefore, repurposing of the drugs started against SARS-CoV-2, due to which several drugs were approved for the treatment of COVID-19 patients. This paper reviewed the treatment regime for COVID-19 through drug repurposing from December 8, 2019 (the day when WHO recognized COVID-19 as a pandemic) until today. We have reviewed all the clinical trials from RECOVERY trials, ACTT-1 and ACTT-2 study group, and other major clinical trial platforms published in highly reputed journals such as NEJM, Lancet, etc. In addition to single-molecule therapy, several combination therapies were also evaluated to understand the treatment of COVID-19 from these significant clinical trials. To date, several lessons have been learned on the therapeutic outcomes for COVID-19. The paper also outlines the experiences gained during the repurposing of therapeutic molecules (hydroxychloroquine, ritonavir/ lopinavir, favipiravir, remdesivir, ivermectin, dexamethasone, camostatmesylate, and heparin), immunotherapeutic molecules (tocilizumab, mavrilimumab, baricitinib, and interferons), combination therapy, and convalescent plasma therapy to treat COVID-19 patients. We summarized that anti-viral therapeutic (remdesivir) and immunotherapeutic (tocilizumab, dexamethasone, and baricitinib) therapy showed some beneficial outcomes. Until March 2021, 4952 clinical trials have been registered in ClinicalTrials.gov toward the drug and vaccine development for COVID-19. More than 100 countries have participated in contributing to these clinical trials. Other than the registered clinical trials (medium to large-size), several small-size clinical trials have also been conducted from time to time to evaluate the treatment of COVID-19. Four molecules showed beneficial therapeutic to treat COVID-19 patients. The short-term repurposing of the existing drug may provide a successful outcome for COVID-19 patients. Therefore, more clinical trials can be initiated using potential anti-viral molecules by evaluating in different phases of clinical trials.

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Resources and computational strategies to advance small molecule SARS-CoV-2 discovery: Lessons from the pandemic and preparing for future health crises

Cited by 20 publications

References 271 publications

COVID-19 infection and neurodegeneration: Computational evidence for interactions between the SARS-CoV-2 spike protein and monoamine oxidase enzymes

COVID-19 infection and neurodegeneration: Computational evidence for interactions between the SARS-CoV-2 spike protein and monoamine oxidase enzymes

Repurposable drugs for SARS-CoV-2 and influenza sepsis with scRNA-seq data targeting post-transcription modifications

The Drug Repurposing for COVID-19 Clinical Trials Provide Very Effective Therapeutic Combinations: Lessons Learned From Major Clinical Studies

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