De novo designed inhibitor has high affinity to four variants of the RBD of S-glycoprotein of SARS-CoV-2 - an in silico study.

ABSTRACT

In the years since the rapid invasion of SARS-CoV-2, the world community has fully understood the extent of the danger of this new pathogen. And also the speed with which he is able to adapt both to humans as a species and to the means of combat that are introduced. However, this has already resulted in millions of lost lives and this situation may worsen in the future, due to the further inevitable evolution of the virus. Accordingly, the need for effective drugs is urgent. In this work, using an iterative approach, we de novo designed a molecule that revealed significant affinity to four variants of SARS-CoV-2 - Wuhan, Omicron, Delta and Cluster 5. More precisely, to their receptor-binding domain of S-glycoprotein, in particular, to the site that is directly involved in the recognition of human ACE2.What is confirmed in particular by the ΔGbind of the complexes of RBD of all four SARS-CoV-2 variants with a potential inhibitor it is in significantly negative values. Along with this, the calculated ADMET parameters can generally be considered acceptable. Accordingly, we believe that the molecule we have designed has a high potential for further development as an effective drug against SARS-CoV-2. However, it currently requires further in vitro and in vivo studies.Communicated by Ramaswamy H. Sarma.