Computational investigation into Nirematrelvir/Ritonavir synergetic efficiency compared with some approved antiviral drugs targeting main protease (Mpro) SARS-CoV-2 Omicron variant

Although the severity of the spread of corona virus has recently decreased. On this day, there is no available effective medication established to treat COVID-19. Combination drug therapy has been recently gained new momentum as an important platform to design and develop several anti-infective agents. In this study, the last FDA-authorized covid-19 therapy ritonavir-boosted nirmatrelvir (Paxlovid) have been the subject to investigate their potential synergetic efficiency in comparison with some selected antiviral drugs through molecular multiple docking, density functional theory (DFT) calculations, physicochemical and pharmacokinetics predicted properties. The multiple docking results revealed the most synergistic affinities for nirmatrelvir with nitonavir drugs against the main protease (Mpro) of omicron variant. LogP, H-bond acceptor and H-bond donor were found as the powerful predicted parameters of nirmatrelvir and ritonavir synergetic drugs. It has been well established that chemical reactivity descriptors displayed the same values for these both drugs. The pharmacokinetic parameters did not exhibit any correlation with the combined compounds affect.

Spike Protein Potential Receptors Study: Comparative Computational Analysis Approach on SARS-CoV-2-AC2/CD147 Complexes

SARS-CoV-2 invades host cells via interaction of its spike protein with the human angiotensin-converting enzyme 2 as the receptor. CD147, as a biomarker for hyperinflammation, was found to be the functional receptor for SARS-CoV-2 and an additional cell entry route. In this paper, we focused our analysis on the initial step of virus infection by comparing the affinity, stability, and specificity of the SARS-CoV-2 spike 1-AC2 and SARS-CoV-2 spike 1-CD147 complexes. Protein-protein docking was utilized for identifying the hotspot residues in the interface of spike protein with AC2 and CD147. The results of binding free energies showed a high affinity of SP1-AC2 complex (-52.97 kcal/mol) compared with SP1-CoV2/CD147 (-35.75 kcal/mol). RMSF values indicate that the spike protein of SARS-CoV-2 RBD is more compatible with binding to the human ACE2 with high flexibility. Computational analysis of binding modes and protein contacts reported that CD147 and ACE2 might be two complementary receptors mediating virus infection and confirmed the experimental results previously. © 2022 by the authors.