SARS-CoV-2 (severe acute respiratory syndrome causing coronavirus 2) caused an epidemic that swept the globe and resulted in large number of casualties. It is still sporadically causing cases and has a long-term impact on the health of once infected individuals. Molnupiravir binds RNA dependent RNA polymerase (RdRp) of SARS-CoV-2 as well as spike protein. In this study, we assessed the mutated spike protein of BA.5 variant and BQ.1.1 subvariant of COVID-19 and tested their binding with it. Multiple sequence and structural alignment of homologous structures revealed highly conserved amino acid residues at the active site of the domain. The molecular docking of Molnupiravir with the active site of the domain, comprised conserved motifs (motif A-G), and exhibited considerable binding affinity against variant and subvariant protein targets. Molnupiravir exhibited stability in its interactions with the Omicron and BQ.1.1 spike proteins, preserving constant engagement within the active site. The protein and Ligand reached An equilibrium with An RMSD of 10.46 Å after 100 nanoseconds, whereas the Ligand measured 8.0 Å. Fluctuations were noted between 40 And 75 nanoseconds, stabilizing from 80 to 100 ns. In simulations including the BQ.1.1 subvariant, the RMSD values demonstrated considerable stability, exhibiting Little variations. The ligand demonstrated flexibility, altering its binding orientation over time, resulting in An average RMSD of 18.72 Å. Herein, investigation of molecular dynamics trajectories elucidated the conformational stability of Molnupiravir, emphasizing its interactions with active residues and the hydrogen bond acceptor and donor environments. The results highlighted the crucial function of protein loops in offering flexibility and enabling ligand binding within the active site. It is concluded that Molnupiravir has the potential to function as an inhibitor of both omicron and its subvariant BQ.1.1.

ORFV, also known as Ecthyma contagiosum, in humans is the Orf virus (ORFV), which mostly infects various wild and domesticated animals. A highly contagious zoonotic viral infection is a major concern to everyone who works with sheep and goats. According to taxonomy, ORFV belongs to the genus Parapoxvirus. People encounter animals, their exposed skin areas usually develop sores. Even though the quantity of infected individuals and appearances are thought to be less dangerous, the pathogenic virus's high fatality rate is still a serious concern. Vaccine construct There is currently no approved vaccine to lessen the epidemiological and clinical burden of this highly contagious illness. Thus, the target proteins of ORFV are used in our current investigation to design and formulate a multi-epitope vaccination using immunoinformatic approaches. Potential T-cell and B-cell epitopes from the two pathogenic proteins of ORFV were tested using selection criteria. The chosen epitopes were then put together using the appropriate adjuvants and linkers. MHC cluster analysis and population coverage of the chosen epitopes were both satisfactory. To maintain the tertiary or quaternary relationships, we used disulfide bonding engineering. Additionally, normal-mode analysis was used to investigate the vaccine protein stability and kinematics. The immunological simulation research of vaccine complexes also yielded substantial findings. Furthermore, the molecular docking demonstrated a greater affinity of −265.85 kcal/mol for toll-like receptor-4 (TLR4). Molecular dynamics simulations resulted in the stability of the complex system with (mean RMSD: 7.7 Å; Rg: 18.6 Å), exhibiting localized flexibility at certain residues. Calculations of binding free energy (ΔG = −456.67 kcal/mol, GBSA; −469.56 kcal/mol, PBSA) indicated highly favorable and spontaneous interactions facilitated by electrostatic and van der Waals forces. Herein, our research findings revealed that the vaccine designs may modulate encouraging immune responses against the pathophysiology of ORFV. Therefore, it can generate a baseline pipeline for the experimentalist for in vivo and in vitro investigations.

Monkeypox virus is a zoonotic virus of the genus Orthopox viruses. It can be transmitted through direct or indirect contact with animals or infected ones. Owing similarity of pathogenesis with smallpox, the same drugs can be used for both viruses, but they are not specific and only help to relieve the symptoms only. Therefore, the absence of antiviral treatment or licensed vaccine highlights an urgent need, especially due to its rapid prevalence. The study screened the library of compounds to retrieve drug-like molecules that can act against monkeypox virus. The highly virulent target gene B8R having uniport ID Q3I8J0 was chosen. Targeting B8R is substantial for global health and can align with SDG 3 and awareness of disease management. The B8R was modelled via Artificial intelligence (AI) AlphaFold method and then exposed to a library of compounds. Complementary interactions in the active site were shown by molecular docking. The Complex-1 had the greatest binding affinity (–8.4 kcal/mol), followed by Complex-2 (–8.1 kcal/mol) and Complex-3 (–7.7 kcal/mol). After 125 ns, Complex-1 reached equilibrium at 7.5 Å RMSD, according to MD simulations, exhibiting stable ligand retention and reliable interactions with crucial residues Gly135 and Lys136. Complex-3 shown intermediate protein stability (6 Å RMSD) but notable ligand fluctuation (48 Å RMSF), while Complex-2 displayed increased protein RMSD (8 Å RMSD) and delayed ligand stabilisation (16 Å RMSF). These results were corroborated by PCA analysis, which showed that Complex-1 exhibits coherent structural development whereas Complex-2 and Complex-3 show scattered and compact trajectories, respectively. Complex-1 promise for Mpox viral inhibition was highlighted by the fact that it was the most stable and dynamically favourable contender overall. The N-terminal follows the folding trend. The insilico analysis not only proposed a potent compound but also provides deep insight into the behavior of protein. The proposed potent compound against this zoonotic virus can be helpful to combat the monkeypox virus by subjecting it further towards experimental investigation.