Docking and other computing tools in drug design against SARS-CoV-2.

The use of computer simulation methods has become an indispensable component in identifying drugs against the SARS-CoV-2 coronavirus. There is a huge body of literature on application of molecular modelling to predict inhibitors against target proteins of SARS-CoV-2. To keep our review clear and readable, we limited ourselves primarily to works that use computational methods to find inhibitors and test the predicted compounds experimentally either in target protein assays or in cell culture with live SARS-CoV-2.

New Hybrid Tetrahydropyrrolo[3,2,1-]quinolin-1-ylidene-2-thioxothiazolidin-4-ones as New Inhibitors of Factor Xa and Factor XIa: Design, Synthesis, and In Silico and Experimental Evaluation.

Despite extensive research in the field of thrombotic diseases, the prevention of blood clots remains an important area of study. Therefore, the development of new anticoagulant drugs with better therapeutic profiles and fewer side effects to combat thrombus formation is still needed. Herein, we report the synthesis and evaluation of novel pyrroloquinolinedione-based rhodanine derivatives, which were chosen from 24 developed derivatives by docking as potential molecules to inhibit the clotting factors Xa and XIa.

Experimentally Validated Novel Factor XIIa Inhibitors Identified by Docking and Quantum Chemical Post-processing.

Antithrombotic agents based on factor XIIa inhibitors can become a new class of drugs to manage conditions associated with thrombosis. Herein, we report identification of two novel classes of factor XIIa inhibitors. The first one is triazolopyrimidine derivatives designed on the basis of the literature aminotriazole hit and identified using virtual screening of the focused library.

New Blood Coagulation Factor XIIa Inhibitors: Molecular Modeling, Synthesis, and Experimental Confirmation.

In the modern world, complications caused by disorders in the blood coagulation system are found in almost all areas of medicine. Thus, the development of new, more advanced drugs that can prevent pathological conditions without disrupting normal hemostasis is an urgent task. The blood coagulation factor XIIa is one of the most promising therapeutic targets for the development of anticoagulants based on its inhibitors.

[Development of antiviral drugs based on inhibitors of the SARS-COV-2 main protease].

Docking and quantum-chemical methods have been used for screening of drug-like compounds from the own database of the Voronezh State University to find inhibitors the SARS-CoV-2 main protease, an important enzyme of the coronavirus responsible for the COVID-19 pandemic. Using the SOL program more than 42000 3D molecular structures were docked into the active site of the main protease, and more than 1000 ligands with most negative values of the SOL score were selected for further processing. For all these top ligands, the protein-ligand binding enthalpy has been calculated using the PM7 semiempirical quantum-chemical method with the COSMO implicit solvent model.

Synthesis, Docking, and In Vitro Anticoagulant Activity Assay of Hybrid Derivatives of Pyrrolo[3,2,1-]Quinolin-2(1)-one as New Inhibitors of Factor Xa and Factor XIa.

Coagulation factor Xa and factor XIa are proven to be convenient and crucial protein targets for treatment for thrombotic disorders and thereby their inhibitors can serve as effective anticoagulant drugs. In the present work, we focused on the structure-activity relationships of derivatives of pyrrolo[3,2,1-]quinolin-2(1)-one and an evaluation of their activity against factor Xa and factor XIa. For this, docking-guided synthesis of nine compounds based on pyrrolo[3,2,1-]quinolin-2(1)-one was carried out.