ABSTRACT
The relevance of coagulation malfunction in COVID-19 (severe coronavirus disease) is ambiguous. Current study aimed to assess the coagulation among SARS-CoV-2 hospitalized patients. A cross sectional study with qualitative approach was conducted among 300 patients who are already diagnosed as COVID 19 compared to 300 apparently healthy control group attended to Red Sea State during study period from April 2020 to April 2021. The Humaclot Due Plus1 coagulation analyser was used to estimate the prothrombin time (PT), activated partial prothrombin time (APTT), and international normalized ratio (INR) (Wiesbaden 1, Germany), adding 25 μL of plasma in cuvette. The study result showed that in COVID-19 patients D.dimer level is high (2000-10000 ng/mL) compared with control group (up to 500 ng/mL). COVID-19 infection cause high D. dimer level which can lead to thrombosis event or bleeding tendency. Abnormal coagulation results were revealed among SARS-CoV-2, with markedly elevated D. dimer.
ABSTRACT
Presently, the world is under the toll of pandemic coronavirus disease-2019 (COVID-19) outbreak caused by SARS-CoV-2. Lack of effective and safe therapeutics has stressed the scientific community for developing novel therapeutics capable of alleviating and stopping this pandemic. Within the presented study, molecular docking, ADME properties and all-atom molecular dynamic (MD) simulation, along with two standard antiviral agents (lopinavir and benzopurpurin-4B), were applied to investigate 15 scalaranes sesterterpenes natural compounds, purified from the Red Sea marine sponge Hyrtios erectus, as potential COVID-19 dual-target inhibitors. Following multi-step docking within COVID-19 main protease and Nsp15 endoribonuclease cavities, nine promising drug-like compounds exhibited higher docking scores as well as better interactions with the target's crucial residues than those of reference ligands. Compounds 2, 6, 11, and 15, were predicted to simultaneously subdue the activity of the two COVID-19 targets. Dynamics behavior of the best-docked molecules, compounds 15 and 6, within COVID-19 target pockets showed substantial stability of ligand-protein complexes as presented via several MD simulation parameters. Furthermore, calculated free-binding energies from MD simulation illustrated significant ligand's binding affinity towards respective target pockets. All provided findings supported the utility of scalarane-based sesterterpenes, particularly compounds 15 and 6, as promising lead candidates guiding the development of effective therapeutics against SARS-CoV-2.