Allosteric binders of ACE2 are promising anti-SARS-CoV-2 agents
Joshua E. Hochuli,Sankalp Jain,Cleber C. Melo-Filho,Zoe L Sessions,Tesia Bobrowski,Jun Kyoung Choe,John Zheng,Richard T. Eastman,Daniel C. Talley,Ganesha Rai,Anton Simeonov,Alexander Tropsha,Eugene N. Muratov,Bolormaa Baljinnyam,Alexey V. Zakharov +14 more
TLDR
Five compounds that bind the human ACE2 protein can interrupt SARS-CoV-2 replication without damaging ACE2’s natural enzymatic function, and serve as a strong starting point for both development of acute treatments for COVID-19 and research into the mechanism of infection.Abstract:
The COVID-19 pandemic has had enormous health, economic, and social consequences. Vaccines have been successful in reducing rates of infection and hospitalization, but there is still a need for an acute treatment for the disease. We investigate whether compounds that bind the human ACE2 protein can interrupt SARS-CoV-2 replication without damaging ACE2’s natural enzymatic function. Initial compounds were screened for binding to ACE2 but little interruption of ACE2 enzymatic activity. This set of compounds was extended by application of quantitative structure-activity analysis, which resulted in 512 virtual hits for further confirmatory screening. A subsequent SARS-CoV-2 replication assay revealed that five of these compounds inhibit SARS-CoV-2 replication in human cells. Further effort is required to completely determine the antiviral mechanism of these compounds, but they serve as a strong starting point for both development of acute treatments for COVID-19 and research into the mechanism of infection. TOC Graphic: Overall study design.read more
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The P132H mutation in the main protease of Omicron SARS-CoV-2 decreases thermal stability without compromising catalysis or small-molecule drug inhibition
Michele Sacco,Yanmei Hu,Maura V Gongora,Flora Meilleur,M. Trent Kemp,Xiujun Zhang,Jun Wang,Yu Chen +7 more
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Butein as a potential binder of human ACE2 receptor for interfering with SARS-CoV-2 entry: a computer-aided analysis
TL;DR: In this article , a subset of natural compounds from the literature that have demonstrated activity in counteracting pathogen infections was screened, using in silico methods, this subset of NATs for searching potential drug candidates able to interfere in the recognition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and its target human angiotensin-converting enzyme 2 (hACE2) receptor, leading to the viral entry.
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