ABSTRACT
The pandemic COVID-19, caused by the organism severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) belongs to the family Coronoviridae has become a serious global healthcare crisis. The biggest demand of the present time is to develop efficacious medication for the treatment of SARS-CoV-2. In the present study, we performed the interaction of 50 flavonoids selected from the Pubchem database, with five efficacious protein targets for SARS-CoV-2: main protease (Mpro), spike glycoprotein-receptor binding domain (SGp-RBD), RNA-dependent RNA polymerase (RdRp), angiotensin converting enzyme-2 (ACE-2) and non-structural protein15 (NSP15, an endonuclease). All the work involve in the present study was accomplished by using Maestro 12.4 (Schrodinger Suite) to obtain the docking scores and ADME-T study result of selected ligands with the five effective target proteins of SARS-CoV-2. Molecular docking-based results indicated that diosmin has the most favorable docking scores-10.16,-11.52,-9.75,-11.25 and-10.25 kcal/mol for the Mpro, SGp-RBD, ACE-2, RdRp and NSP-15 protein targets and had acceptable drug suitability as a therapeutic agent against COVID-19. The structure of this compound can be further useful to medicinal chemists, pharmacologists, and clinicians for efficiently discovering or developing effective drugs to cure COVID-19.
ABSTRACT
Background: The mortality of kidney transplant recipients (KTR) affected with coronavirus disease-2019 (COVID-19) is reported to be higher than the general population. There is a scarcity of data on the pattern and outcome of COVID-19 in KTRs in developing country like India. Materials and Methods: It was a retrospective study conducted in a tertiary care center in North India. The detailed data on the Covid-19 affected KTR admitted to our center from March 2020 to March 2021 was obtained from computerized records. Clinical and biochemical characteristics of the survivors and nonsurvivors were studied. The factors affecting the mortality in this cohort were analyzed. Results: Of the 35 participants, 25 (71.4%) were males. The mean age was 53.06 & PLUSMN;11.84 years. Overall, mortality was 17.1% (Six out of 35). There was a significant difference in the oxygen saturation at presentation, computed tomography severity scores, level of inflammatory markers, level of serum albumin, and the absolute lymphocyte count (ALC) between the survivors and nonsurvivors (P < 0.05). On univariate regression analysis, serum C-reactive protein, ferritin, albumin, and ALC were found to be significantly predicting mortality in COVID-19 affected KTR. Conclusions: Mortality rate in COVID-19 affected KTR is higher than in the general population. Clinical, biochemical, and radiological parameters can be helpful in predicting the adverse outcome.
ABSTRACT
Objective: Recent pandemic caused by the SARS-CoV-2, first described in Wuhan city of China in December 2019, spread widely in almost all the countries of the world. Coronavirus (COVID-19) led to the unexpected death of many people and caused a severe economic loss in a number of countries. Virtual screening based on molecular docking, drug-likeness prediction, and in silico ADMET studies are some of the effective tools for the identification of small molecules as novel antiviral drugs to treat diseases. Methods: In the current study, virtual screening was performed through molecular docking for identi-fying potent inhibitors against Mpro enzyme from the ZINC library for the possible treatment of the COVID-19 pandemic. Interestingly, some compounds have been identified as possible anti-covid-19 agents for future research. A total of 350 compounds were screened based on their similarity score with reference compound X77 from ZINC data bank and were subjected to docking with crystal struc-ture available of Mpro enzyme. These compounds were then filtered by their in silico ADME-Tox and drug-likeness prediction values. Results: Out of these 350 screened compounds, 10 compounds were selected based on their docking score and best-docked pose in comparison to the reference compound X77. In silico ADME-Tox and drug likeliness predictions of the top compounds were performed and showed excellent results. All the 10 screened compounds showed a significant binding pose with the target main protease (Mpro) enzyme and satisfactory pharmacokinetic and toxicological properties. Conclusion: Based on these results, it is suggested that the identified compounds may be considered for therapeutic development against the COVID-19 virus and can further be evaluated for in vitro ac-tivity, preclinical, clinical studies, and formulated in a suitable dosage form to maximize their bioa-vailability. ©2021 Bentham Science Publishers.
ABSTRACT
The recent pandemic caused by SARS-CoV-2 is a major health concern for the entire world. Fast transmission and the mortality rate of this disease is a serious threat to human society. By looking into its seriousness finding medication against this disease is the biggest task of the present time. In the present study, computational approach is used to find effective compounds against SARS-CoV-2 infections. 1452 compounds having potential antiviral activity were selected from PubChem database to search potential inhibitors for the therapeutic targets of SARS-CoV-2. Molecular docking and absorption, distribution, metabolism, elimination and toxicity (ADMET) properties study were performed using Maestro 12.4 (Schrodinger Suite). All the selected compounds were funneled down to six compounds which are found to be effective against all the five targets of SARS-CoV-2. Among six compounds, compound C6 is exhibited excellent docking score -8.93, -8.21, -7.93, -6.73 kcal/mol with main protease (Mpro), angiotensin-converting enzyme-2 (ACE2), RNA dependent RNA polymerase (RdRp), and endoribonuclease (NSP15) target proteins respectively. © 2021. The Author(s). All Rights Reserved.