Exploring the Binding Efficacy of Ivermectin Against the Key Proteins of SARS-CoV-2 Pathogenesis: an in silico Approach

Abstract

Aim: COVID-19 is currently the biggest threat to mankind. Recently, ivermectin (a US FDA-approved antiparasitic drug) has been explored as an anti-SARS-CoV-2 agent. Herein, we have studied the possible mechanism of action of ivermectin using in silico approaches. Materials & methods: Interaction of ivermectin against the key proteins involved in SARS-CoV-2 pathogenesis were investigated through molecular docking and molecular dynamic simulation. Results: Ivermectin was found as a blocker of viral replicase, protease and human TMPRSS2, which could be the biophysical basis behind its antiviral efficiency. The antiviral action and ADMET profile of ivermectin was on par with the currently used anticorona drugs such as hydroxychloroquine and remdesivir. Conclusion: Our study enlightens the candidature of ivermectin as an effective drug for treating COVID-19.

Comparative study of the interaction of ivermectin with proteins of interest associated with SARS-CoV-2: A computational and biophysical approach

“…This kinetic aspect is favored in HB1a and HB1b for the cellular and viral proteins studied, respectively. A differential activity that has already been reported for these compounds both at the energy level and in terms of their particular affinity for related cellular and viral proteins [ 91 ].…”

In silico-based Discovery of New Potential Drugs Targeting Severe Acute Respiratory Syndrome Coronavirus 2 Spike Glycoprotein

“…They also observed the strong binding of SARS-CoV-2 S protein with ACE2 receptors from both human and bat origin (as phylogenetically close), indicating its usefulness in adopting S protein-, ACE2-, or TLR-guided intervention strategy against COVID-19 disease [42]. Binding of ivermectin was studied against the key proteins of SARS-CoV-2 pathogenesis using molecular docking and MD simulations [43]. This study predicted the blocking actions of ivermectin against viral replicase, protease, and human transmembrane serine protease 2 (TMPRSS2) supporting its utility in COVID treatment.…”

Repositioning Ivermectin for Covid-19 treatment: Molecular mechanisms of action against SARS-CoV-2 replication

“…IVM may achieve this by targeting the interaction between S protein and host ACE2, allowing a conformational change of the S protein and guiding the virus towards an abortive infection due to its inability to infiltrate the host cells [73] . While the exact mechanism behind IVM has yet to be determined, docking studies have demonstrated the ability of IVM to attach to leucine 91 in S protein and histidine 378 of the SARS-CoV-2-ACE2 receptor complex [74] .…”