Study of Oxadiazole derivatives as precursor for multi-functional inhibitor to SARS-CoV-2: A detailed virtual screening analysis

Vikash Kumar, Sumit Kumar — Thu, 01 Feb 2024 00:00:00 +0000

SARS-CoV-2, the virus responsible for the COVID-19 pandemic, is highly contagious and has caused widespread loss of life. In the quest to find effective antiviral agents, attention has turned to oxadiazole derivatives, which are known for their potential antiviral properties in such as CoViTris2020, ChloViD2020, etc. To evaluate their effectiveness, molecular docking and molecular dynamics simulations are conducted for various oxadiazole derivative in interactions with critical proteins involved in the viral infection process. These proteins encompass transmembrane-serine-2 (TMPRSS2), 3-chymotrypsin-like-protease (3CLpro), angiotensin-converting-enzyme-2 (ACE2), and papain-like-protease (PLpro). The study shows that the oxadiazole derivatives exhibited their most stable complexes when interacting with TMPRSS2 in comparison to 3CLpro, ACE2, and PLpro. In particular, Oxa8 displayed a binding energy of -6.52 kcal/mol with TMPRSS2. In contrast, the binding energies with ACE2, 3CLpro, and PLpro were -5.74, -4.56, and -5.56 kcal/mol, respectively. RMSD analysis during MD simulations demonstrated that the complex structure remained consistently stable. During the initial 2 ns, the RMSD value for the ligand concerning its interaction with the protein backbone hovered around 2 Å, indicating a sustained level of structural stability. In conclusion, this study suggests that oxadiazole derivative Oxa8 holds promise as a potential inhibitor of SARS-CoV-2, particularly due to its strong binding affinity with TMPRSS2 and its enduring structural stability observed in molecular dynamics simulations.

Cytotoxicity screening of 114 Mongolian plant extracts on liver, colon, breast, and cervix cancer cell lines

Wed, 27 Mar 2024 00:00:00 +0000

A total of 114 Mongolian plant species were subjected to cytotoxicity screening against liver (HepG2), colon (HCT116), breast (MCF7), and cervical (HeLa) cancer cell lines. Among them, ethanolic extracts of Androsace incana, Artemisia rutifolia, Saussurea amara, and Inula salsoloides exhibited remarkable cytotoxicity, with IC₅₀ values below 1.5 μg/mL against at least 2 tested cell lines when treated for 48 hours. Erysimum flavum, Juniperus sibirica, and Stellaria dichotoma demonstrated selective cytotoxicity against specific cancer cell lines. Extracts from 23 plant species, such as Artemisia xerophytica, Ajania trifida, Melandrium brachypetalum, Brachanthemum mongolicum, and Rhinanthus songaricus, showed moderate toxicity. Further research on the phytochemicals and biological activities of these species is crucial for a deeper understanding and potential applications. These screening results of the cytotoxic effects of numerous Mongolian plants could establish a foundational dataset for subsequent comprehensive studies on the screened plants.

Mongolian Journal of Chemistry

Study of Oxadiazole derivatives as precursor for multi-functional inhibitor to SARS-CoV-2: A detailed virtual screening analysis

Cytotoxicity screening of 114 Mongolian plant extracts on liver, colon, breast, and cervix cancer cell lines