An in silico LLPS perturbation approach in the design of a novel SARS-CoV-2 spike receptor-binding domain inhibitor

Abstract

The reversible process where a homogenous fluid de-mixes into two distinctively separate liquid phases is referred to as LLPS (Liquid-liquid phase separation). The resulting liquid is made up of one dilute phase and one condensed phase. An increasing number of studies have shown that the liquid-liquid phase separation is an important principle that underlies intracellular organization in biological systems, forming liquid condensates without a membrane envelope, otherwise known as MLOs (membraneless organelles). Such organelles include the P bodies, nucleolus and stress granules. Moreover, the regulation of many other biological processes such as signal transduction, chromatin rearrangement and RNA metabolism have been linked to the liquid-liquid phase separation.

MasitinibL shows promise as a drug-like analog of masitinib that elicits comparable SARS-Cov-2 3CLpro inhibition with low kinase preference

“…This challenge necessitates the search for broad-spectrum antivirals that will also be effective against possible future variants. Tackling this challenge will require targeting a highly conserved and stable region of the SARS-CoV-2 virus core protein machinery 8 . The main viral protease, 3CLpro (also known as Mpro or nonstructural protein 5 [nsp5]), is responsible for cleaving translated proteins into active proteins 9 .…”