ABSTRACT
Remdesivir and hydroxychloroquine derivatives form two important classes of heterocyclic compounds. They are known for their anti-malarial biological activity. This research aims to analyze the physicochemical properties of remdesivir and hydroxychloroquine compounds by the computational approach. DFT, docking, and POM analyses also identify antiviral pharmacophore sites of both compounds. The antiviral activity of hydroxychloroquine compound's in the presence of zinc sulfate and azithromycin is evaluated through its capacity to coordinate transition metals (M = Cu, Ni, Zn, Co, Ru, Pt). The obtained bioinformatic results showed the potent antiviral/antibacterial activity of the prepared mixture (Hydroxychloroquine/Azithromycin/Zinc sulfate) for all the opportunistic Gram-positive, Gram-negative in the presence of coronavirus compared with the complexes Polypyridine-Ruthenium-di-aquo. The postulated zinc(II) complex of hydroxychloroquine derivatives are indeed an effective antibacterial and antiviral agent against coronavirus and should be extended to other pathogens. The combination of a pharmacophore site with a redox [Metal(OH2)2] moiety is of crucial role to fight against viruses and bacteria strains. [Formula: see text]Communicated by Ramaswamy H. Sarma.
ABSTRACT
SARS-CoV-2 has rapidly emerged as a global pandemic with high infection rate. At present, there is no drug available for this deadly disease. Recently, Mpro (Main Protease) enzyme has been identified as essential proteins for the survival of this virus. In the present work, Lipinski's rules and molecular docking have been performed to identify plausible inhibitors of Mpro using food compounds. For virtual screening, a database of food compounds was downloaded and then filtered using Lipinski's rule of five. Then, molecular docking was accomplished to identify hits using Mpro protein as the target enzyme. This led to identification of a Spermidine derivative as a hit. In the next step, Spermidine derivatives were collected from PubMed and screened for their binding with Mpro protein. In addition, molecular dynamic simulations (200 ns) were executed to get additional information. Some of the compounds are found to have strong affinity for Mpro, therefore these hits could be used to develop a therapeutic agent for SARS-CoV-2.
ABSTRACT
In the present work, an extensive QSAR (Quantitative Structure Activity Relationships) analysis of a series of peptide-type SARS-CoV main protease (MPro) inhibitors following the OECD guidelines has been accomplished. The analysis was aimed to identify salient and concealed structural features that govern the MPro inhibitory activity of peptide-type compounds. The QSAR analysis is based on a dataset of sixty-two peptide-type compounds which resulted in the generation of statistically robust and highly predictive multiple models. All the developed models were validated extensively and satisfy the threshold values for many statistical parameters (for e.g. R2 â= â0.80-0.82, Q2 loo â= â0.74-0.77, Q 2 LMO â= â0.66-0.67). The developed QSAR models identified number of sp2 hybridized Oxygen atoms within seven bonds from aromatic Carbon atoms, the presence of Carbon and Nitrogen atoms at a topological distance of 3 and other interrelations of atom pairs as important pharmacophoric features. Hence, the present QSAR models have a good balance of Qualitative (Descriptive QSARs) and Quantitative (Predictive QSARs) approaches, therefore useful for future modifications of peptide-type compounds for anti- SARS-CoV activity.