A Study of Drug Repurposing to Identify SARS-CoV-2 Main Protease (3CLpro) Inhibitors

Abstract

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wreaked havoc all over the world. Although vaccines for the disease have recently become available and started to be administered to the population in various countries, there is still a strong and urgent need for treatments to cure COVID-19. One of the safest and fastest strategies is represented by drug repurposing (DRPx). In this study, thirty compounds with known safety profiles were identified from a chemical library of Phase II-and-up compounds through a combination of SOM Biotech’s Artificial Intelligence (AI) technology, SOMAIPRO, and in silico docking calculations with third-party software. The selected compounds were then tested in vitro for inhibitory activity against SARS-CoV-2 main protease (3CLpro or Mpro). Of the thirty compounds, three (cynarine, eravacycline, and prexasertib) displayed strong inhibitory activity against SARS-CoV-2 3CLpro. VeroE6 cells infected with SARS-CoV-2 were used to find the cell protection capability of each candidate. Among the three compounds, only eravacycline showed potential antiviral activities with no significant cytotoxicity. A further study is planned for pre-clinical trials.

New highly selective antivirals for Chikungunya Virus identified from the screening of a drug-like compound library

“…Eravacycline, is a synthetic fourth generation tetracycline that works via inhibition of the 30S ribosomal subunit and was initially approved in August 2018 to treat complicated intraabdominal infections [35]. It was reported to be active against SARS-CoV-2 targeting the viral main cysteine-protease 3CLpro [36] and, using computational approaches, it was suggested as a potential drug molecule against monkeypox DdRp [37].…”

“…The copyright holder for this preprint this version posted May 17, 2024. ; https://doi.org/10.1101/2024.05.17.594707 doi: bioRxiv preprint 3CLpro [36] and, using computational approaches, it was suggested as a potential drug molecule against monkeypox DdRp [37].…”

The activity of bioactive compounds from bidara upas (Merremia mammosa (Lour) Hall. f.) as an inhibitor of SARS-CoV2 entry stage: In silico study

“…Three of the compounds, such as cynarine, phellodensin F and gemixanthone A, were flavonoids that may interact with the substratebinding and catalytic site amino acids of TMPRSS2 (Hussain et al, 2020). Cynarine was known to have strong inhibitory activity against SARS-CoV-2's main protease (3CLpro or Mpro), but this compound is quickly metabolised after oral administration (Jo et al, 2022). Gemixanthone A was also known to have an activity to inhibit the SARS-CoV-2 spike protein with MMGBSA value -60.2985.…”