Computational Chemistry to Repurposing Drugs for the Control of COVID-19

Abstract

Thus far, in 2021, 219 countries with over 175 million people have been infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a positive sense, single-stranded RNA virus, and is the causal agent for coronavirus disease (COVID-19). Due to the urgency of the situation, virtual screening as a computational modeling method offers a fast and effective modality of identifying drugs that may be effective against SARS-CoV-2. There has been an overwhelming abundance of molecular docking against SARS-CoV-2 in the last year. Due to the massive volume of computational studies, this systematic review has been created to evaluate and summarize the findings of existing studies. Herein, we report on computational articles of drugs which target, (1) viral protease, (2) Spike protein-ACE 2 interaction, (3) RNA-dependent RNA polymerase, and (4) other proteins and nonstructural proteins of SARS-CoV-2. Based on the studies presented, there are 55 identified natural or drug compounds with potential anti-viral activity. The next step is to show anti-viral activity in vitro and translation to determine effectiveness into human clinical trials.

Aged Population and Immunocompromised Patients: Impact on SARS-CoV-2 Variants and Treatment Outcomes

“…Since the advent of the COVID-19 pandemic, the application of bioinformatics and drug repurposing has accelerated the research efforts for COVID-19 drug discovery. Different chembioinformatic approaches (fragment-based, structure-based, and ligand-based modelling strategies), and immunobioinformatics may be useful hall markers to prioritize the drug candidate and vaccine candidate, respectively, for further experiments [32][33][34]. Computational drug repurposing (repositioning) is an effective approach to identifying novel drug-target interactions using the drugs already known to be safe, which provides the advantages of significantly reducing the time for drug development and reduced failure rate [35].…”

An integrated metabolomic and proteomic approach for the identification of covalent inhibitors of the main protease (Mpro) of SARS-COV-2 from crude natural extracts

“…Recently considerable research, based on virtual screening campaigns and HTS tests aimed at identifying from approved drugs and known natural compounds those able to bind the SARS-CoV-2 protease as a target for potential anti-viral activity, has been carried out [22]; the most intriguing aspect is the high number of identified natural compounds acting as M pro inhibitors, indicating that plants are a valuable source J o u r n a l P r e -p r o o f of bioactive compounds, mostly found to be tightly bound to the very crucial key residue of Cys145, thus inhibiting SARS-CoV-2 replication and proliferation in the host [22,23]. While this approach can be advantageous in terms of reducing costs and study time, the downside of this approach is its limited explorative potential, being as it is confined to the use of what is known: these investigations rely on searching chemical databases and libraries, meaning that they only consider previously structurally-clarified and isolated derivatives; a great advance in the hit identification strategy would be to set-up an analytical strategy aimed at exploring not isolated or even unknown compounds and hence based on un-deconvoluted mixtures of compounds.…”

A computational simulation appraisal of banana lectin as a potential anti-SARS-CoV-2 candidate by targeting the receptor-binding domain

“…Researchers are exploring repurposing antiviral drugs, such as lopinavir, ritonavir, nelfinavir, remdesivir, favipiravir, ribavirin, sofosbuvir, chloroquine, hydroxychloroquine, and azithromycin, to target key SARS-CoV-2 proteins and inhibit the virus [ 7 , 8 ]. Ivermectin, an FDA-approved antiparasitic drug, has shown in vitro antiviral activity against SARS-CoV-2, but requires further research to confirm its efficacy and safety for COVID-19 treatment [ 9 ].…”