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SARS-CoV-2 is a new strain of Coronavirus that caused the pneumonia outbreak in Wuhan, China and has spread to over 200 countries of the world. It has received worldwide attention due to its virulence and high rate of infection. So far, several drugs have experimented against SARS-CoV-2, but the failure of these drugs to specifically interact with the viral protease necessitates urgent measure to boost up researches for the development of effective therapeutics against SARS-CoV-2. Papain-like protease (PLpro) of the viral polyproteins is essential for maturation and infectivity of the virus, making it one of the prime targets explored for SARS-CoV-2 drug design. This study was conducted to evaluate the efficacy of ~ 50,000 natural compounds retrieved from IBS database against COVID-19 PLpro using computer-aided drug design. Based on molecular dock scores, molecular interaction with active catalytic residues and molecular dynamics (MD) simulations studies, STOCK1N-69160 [(S)-2-((R)-4-((R)-2-amino-3-methylbutanamido)-3-(4-chlorophenyl) butanamido) propanoic acid hydrochloride] has been proposed as a novel inhibitor against COVID-19 PLpro. It demonstrated favourable docking score, the free energy of binding, interacted with key amino acid residues necessary for PLpro inhibition and also showed significant moderation for parameters investigated for ADME/tox (Adsorption, distribution, metabolism, excretion and toxicological) properties. The edge of the compound was further established by its stability in MD simulation conducted for 30 ns employing GROMACS software. We propose that STOCK1N-69160 is worth further investigation for preventing SARS-CoV-2. Graphic abstract

BackgroundThe physiopathologies of many neurologic diseases are characterized by related biochemical dysfunctions that could be explored as drug targets. This study evaluated the effect of a methanol leaf extract of Antiaris africana (MEA) on critical bioindices of Parkinsonism and related neurologic dysfunctions in rats with rotenone-induced neurotoxicity.MethodsAnimals were administered 50 or 100 mg/kg MEA for 14 consecutive days. Rotenone (1.5 mg/kg) was administered three times per day on days 13 and 14. Coenzyme Q10 (5 mg/kg) was the reference drug. Complex I activity, dopamine level, activities of acetylcholinesterase, myeloperoxidase, Na+/K+ ATPase and glutamine synthetase, as well as oxidative stress indices were evaluated at the end of the period of treatment.ResultsRotenone-intoxicated group showed disruption of complex 1 activity, dopamine level, and glutamine synthetase activity with negative alterations to activities of acetylcholinesterase, myeloperoxidase, and Na+/K+ ATPase as well as heightened cerebral oxidative stress. MEA restored brain mitochondria functionality, mitigated altered neurochemical integrity, and ameliorated cerebral oxidative stress occasioned by rotenone neurotoxicity. The activity of A. Africana was comparable with that of 5 mg/kg coenzyme Q10.ConclusionsThese results indicated that A. africana displayed therapeutic potential against Parkinsonism and related neurologic dysfunctions and support its ethnobotanical use for the treatment of neurologic disorders.

BackgroundThe physiological functions of the testis and spleen can be affected through several cellular and molecular mechanisms such as the generation of reactive oxygen species (ROS) that causes oxidative stress. This study aimed at investigating the protective effect of catechin, quercetin, and taxifolin in rotenone-induced testicular and splenetic toxicity.MethodsMale Wistar rats were administered with 1.5 mg/kg rotenone (s.c.) for 10 days followed by post-treatment with catechin (5, 10, or 20 mg/kg), quercetin (5, 10, or 20 mg/kg), and taxifolin (0.25, 0.5, or 1.0 mg/kg) for 3 days (s.c.), followed by estimation of biochemical markers of oxidative stress, inflammatory activities, and tissue damage in testes and spleen.ResultsExposure of rats to rotenone caused reduced body weight gain, increased organ weight, decreased glutathione level and activities of glutathione transferase and superoxide dismutase, enhanced lipid peroxidation, and increased activities of prooxidant/proinflammatory enzymes and lactate dehydrogenase, which were mitigated by post-treatment with flavonoids. In general, quercetin and taxifolin showed better activity than catechin.ConclusionsCatechin, quercetin, and taxifolin ameliorated rotenone-induced weight disturbances and oxidative damage in rats, indicating their potential relevance in toxicant and pesticide-induced tissue injury.