Nirmatrelvir, Structural and molecular interaction landscape, Mpro-nirmatrelvir complex, SARS-CoV-2, Infectious and parasitic diseases, RC109-216, Public aspects of medicine, RA1-1270

Background: Several therapeutics have been developed and approved against SARS-CoV-2 occasionally; nirmatrelvir is one of them. The drug target of nirmatrelvir is Mpro, and therefore, it is necessary to comprehend the structural and molecular interaction of the Mpro-nirmatrelvir complex. Methods: Integrative bioinformatics, system biology, and statistical models were used to analyze the macromolecular complex. Results: Using two macromolecular complexes, the study illustrated the interactive residues, H-bonds, and interactive interfaces. It informed of six and nine H-bond formations for the first and second complex, respectively.The maximum bond length was observed as 3.33 Å. The ligand binding pocket's surface area and volume were noted as 303.485 Å2 and 295.456 Å3 for the first complex and 308.397 Å2 and 304.865 Å3 for the second complex. The structural proteome dynamics were evaluated by analyzing the complex's NMA mobility, eigenvalues, deformability, and B-factor. Conversely, a model was created to assess the therapeutic status of nirmatrelvir. Conclusions: Our study reveals the structural and molecular interaction landscape of Mpro-nirmatrelvir complex. The study will guide researchers in designing more broad-spectrum antiviral molecules mimicking nirmatrelvir, which assist in fighting against SARS-CoV-2 and other infectious viruses. It will also help to prepare for future epidemics or pandemics.