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

• Published in: Journal of the Indian Chemical Society Vol. 100; no. 3; p. 100891
• Main Authors: Makhloufi, Abdesselam, Ghemit, Rima, El Kolli, Meriem, Baitiche, Milad
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.03.2023
• Subjects: ADME; DFT; Multi docking; Nirmatrelvir/Ritonavir; Synergetic drugs; Nirmatrelvir/Ritonavir; Multi docking; DFT; ADME; Synergetic drugs
• ISSN: 0019-4522
• DOI: 10.1016/j.jics.2023.100891

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. [Display omitted] •The combination efficacy of the nirmatrelvir/ritonavir ‘Paxolivid’ medication was investigated.•A comparative study of antiviral drugs affinities against omicron Mpro of SARS-2 was realized.•Physicochemical and pharmacokinetics properties and global reactivity descriptors were calculated.•The correlation between synergetic dugs effect was analyzed.