Rilpivirine inhibits SARS-CoV-2 protein targets: A potential multi-target drug.

BACKGROUND: COVID-19 disease caused by SARS-CoV-2 is lacking efficient medication although certain medications are used to relief its symptoms. OBJECTIVES: We tested an FDA-approved antiviral medication namely rilpivirine to find a drug against SARS-CoV-2. METHODS: The inhibition of rilpivirine against multiple SARS-CoV-2 therapeutic targets was studied using in silico method. The binding attraction of the protein-ligand complexes were calculated using molecular docking analysis. RESULTS: Docking rilpivirine with main protease (Mpro), papin like protease (PLpro), sprike protein (Spro), human angiotensin converting enzyme-2 (ACE2), and RNA dependent-RNA polymerase (RdRp) yielded binding energies of -8.07, -8.40, -7.55, -9.11, and -8.69 kcal/mol, respectively. The electrostatic interaction is the key force in stabilizing the RdRp-rilpivirine complex, while van der Waals interaction dominates in the ACE2 rilpivirine case. Our findings suggest that rilpivirine can inhibit SARS-CoV-2 replication by targeting not only ACE2, but also RdRp and other targets, and therefore, it can be used to invoke altered mechanisms at the pre-entry and post-entry phases. CONCLUSION: As a result of our in silico molecular docking study, we suggest that rilpivirine is a compound that could act as a powerful inhibitor against SARS-CoV-2 targets. Although in vitro and in vivo experiments are needed to verify this prediction we believe that this antiviral drug may be used in preclinical trials to fight against SARS coronavirus.

In silico prediction of mozenavir as a potential drug for SARS-CoV-2 infection via binding multiple drug targets.

Since the epidemic began in November 2019, no viable medicine against SARS-CoV-2 has been discovered. The typical medication discovery strategy requires several years of rigorous research and development as well as a significant financial commitment, which is not feasible in the face of the current epidemic. Through molecular docking and dynamic simulation studies, we used the FDA-approved drug mezonavir against the most important viral targets, including spike (S) glycoprotein, Transmembrane serine protease 2 (TMPRSS2), RNA-dependent RNA polymerase (RdRp), Main protease (Mpro), human angiotensin-converting enzyme 2 (ACE-2), and furin. These targets are critical for viral replication and infection propagation because they play a key role in replication/transcription and host cell recognition. Molecular docking revealed that the antiviral medication mozenavir showed a stronger affinity for SARS-CoV-2 target proteins than reference medicines in this investigation. We discovered that mozenavir increases the complex's stability and validates the molecular docking findings using molecular dynamics modeling. Furin, a target protein of COVID-19, has a greater binding affinity (-12.04 kcal/mol) than other COVID-19 target proteins, forming different hydrogen bonds and polar and hydrophobic interactions, suggesting that it might be used as an antiviral treatment against SARS-CoV-2. Overall, the present in silico results will be valuable in identifying crucial targets for subsequent experimental investigations that might help combat COVID-19 by blocking the protease furin's proteolytic activity.

Phenolic compounds as promising drug candidates against COVID-19 - an integrated molecular docking and dynamics simulation study.

Piper was used to cure certain human afflictions. It has various biological processes in literary works. Our work aims to identify and to explain the molecular base in silico in phytoderived anti-viral compounds in Piper nigrum against the major protease enzyme COVID-19. The thesis includes docking and molecular dynamic modelling review of 8 phenolic compounds from Piper extracted from the PubMed database. Docking analysis with Autodock programme was conducted. Our analysis reveals that the two Piper phytochemicals are very susceptible to the COVID-19 major protease enzyme. These phyto-compounds from piper may use contemporary techniques to create a stable drug or help the detection of lead. In order to assess their efficacy against COVID-19, identified hit compounds can be taken further in vitro and in vivo tests.