Abstract
The coronavirus disease-2019 (COVID-19) pandemic, caused by the pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), started in China during late 2019 and swiftly spread worldwide. Since COVID-19 emergence, many therapeutic regimens have been relentlessly explored, and although two vaccines have just received emergency use authorization by different governmental agencies, antiviral therapeutics based neutralizing antibodies and small-drug inhibitors can still be vital viable options to prevent and treat SARS-CoV-2 infections. The viral spike glycoprotein (S-protein) is the key molecular player that promotes human host cellular invasion via recognition of and binding to the angiotensin-converting enzyme 2 gene (ACE2). In this work, we report the results obtained by mutating in silico the 18 ACE2 residues and the 14 S-protein receptor binding domain (S-RBDCoV-2) residues that contribute to the receptor/viral protein binding interface. Specifically, each wild-type protein–protein interface residue was replaced by a hydrophobic (isoleucine), polar (serine and threonine), charged (aspartic acid/glutamic acid and lysine/arginine), and bulky (tryptophan) residue, respectively, in order to study the different effects exerted by nature, shape, and dimensions of the mutant amino acids on the structure and strength of the resulting binding interface. The computational results were next validated a posteriori against the corresponding experimental data, yielding an overall agreement of 92%. Interestingly, a non-negligible number of mis-sense variations were predicted to enhance ACE2/S-RBDCoV-2 binding, including the variants Q24T, T27D/K/W, D30E, H34S7T/K, E35D, Q42K, L79I/W, R357K, and R393K on ACE2 and L455D/W, F456K/W, Q493K, N501T, and Y505W on S-RBDCoV-2, respectively.
Highlights
The coronavirus disease-2019 (COVID-19) pandemic, caused by the pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), started in China during late 2019 and swiftly spread worldwide
Our previous molecular dynamics (MD) simulations have revealed that the main role of the angiotensin-converting enzyme 2 gene (ACE2) wild-type residue Q24, located at the periphery of the receptor/S-RBDCoV‐2 binding interface, is to anchor N487 on the S-RBDCoV‐2 via a stable H-bond (3.03 ± 0.18 Å), along with establishing a few weaker contact interactions (CIs) with G476 and Y489 on the viral protein.[25]
While vaccines directed against this deadly pathogens are becoming available, the repurposing of clinically approved drugs might offer a further, fast lane to anti-COVID-19 effective therapies,[38−41] whereas alternative approaches to target ACE2 and possibly other host cellular and/or pathogen proteins could result in active therapeutic and/or prophylactic agents against viral infection.[42−45] All these alternative strategies might further provide early protection against viral infection by blocking host cell−viral interaction, and reduce the associated severe pathological symptoms; extensive in vitro and in vivo experimental campaigns are unconditionally mandatory before such treatments can be translated into the clinics
Summary
The coronavirus disease-2019 (COVID-19) pandemic, caused by the pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), started in China during late 2019 and swiftly spread worldwide. The Coronavirus Disease 2019 (COVID-19) is a contagious infection caused by the severe acute respiratory syndrome (SARS) coronavirus (CoV) 2 (SARS-CoV-2).[1] The first case was identified in Wuhan, China, in December 2019,2 and, since it has been spreading worldwide leading to the currently ongoing pandemic.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
