The discovery of drugs capable of inhibiting SARS-CoV-2 is a priority for human beings due to the severity of the global health pandemic caused by COVID-19. To this end, repurposing of FDA-approved drugs such as NSAIDs against COVID-19 can provide therapeutic alternatives that could be utilized as an effective safe treatment for COVID-19. The anti-inflammatory activity of NSAIDs is also advantageous in the treatment of COVID-19, as it was found that SARS-CoV-2 is responsible for provoking inflammatory cytokine storms resulting in lung damage. In this study, 40 FDA-approved NSAIDs were evaluated through molecular docking against the main protease of SARS-CoV-2. Among the tested compounds, sulfinpyrazone 2, indomethacin 3, and auranofin 4 were proposed as potential antagonists of COVID-19 main protease. Molecular dynamics simulations were also carried out for the most promising members of the screened NSAID candidates (2, 3, and 4) to unravel the dynamic properties of NSAIDs at the target receptor. The conducted quantum mechanical study revealed that the hybrid functional B3PW91 provides a good description of the spatial parameters of auranofin 4. Interestingly, a promising structure–activity relationship (SAR) was concluded from our study that could help in the future design of potential SARS-CoV-2 main protease inhibitors with expected anti-inflammatory effects as well. NSAIDs may be used by medicinal chemists as lead compounds for the development of potent SARS-CoV-2 (Mpro) inhibitors. In addition, some NSAIDs can be selectively designated for treatment of inflammation resulting from COVID-19.

The global breakout of COVID-19 and raised death toll has prompted scientists to develop novel drugs capable of inhibiting SARS-CoV-2.

S1: 2D and 3D interactions of the identified herbal drugs and docked N3 inhibitor into the N3 inhibitor binding site of Covid-19 main protease (3CLpro) (6LU7). No. Herbal drug 2D protein interactions 3D protein interactions 1 Glycyrrhizin S4: Receptor interactions and binding energies of the identified herbal drugs and Umifenovir into Umifenovir binding site of COVID-19 Spike protein (6ZCZ). No. Herbal drug S a Kcal/mol RMSD b Amino acid bond Distance A ֯ Glycyrrhizin -6.9575 2.4596 SER 373/H-donor TRP 436/H-pi 3.03 4.58 Lycorine -4.7293 1.4725 TRP 436/H-pi 4.51 Puerarin -5.5529 2.1709 TRP 436/H-acceptor ASN 343/H-acceptor ASN 437/pi-H 3.07 3.10 3.72 Daidzein -4.8154 1.1488 ASN 440/H-donor 2.92 Daidzin -6.4474 1.9450 SER 371/H-donor 3.06 Salvianolic acid B -7.4614

Hydroxyethylamine and hydroxyethylene moieties of β-blockers exert potential SARS-CoV-2 inhibitory effects: rational-based design and in silico, in vitro, and SAR Studies.

FMS-like tyrosine kinase 3 (FLT3) mutations occur in approximately 30% of acute myeloid leukemia (AML) patients. In the current study, the oxindole chemotype is employed as a structural motif for the design of new FLT3 inhibitors as potential hits for AML irradiation.Cell-based screening was performed with 18 oxindole derivatives and 5a-c inhibited 68%-73% and 83%-91% of internal tandem duplication (ITD)-mutated MV4-11 cell growth for 48-and 72-h treatments while only 0%-2% and 27%-39% in wild-type THP-1 cells. The most potent compound 5a inhibited MV4-11 cells with IC 50 of 4.3 μM at 72 h while it was 8.7 μM in THP-1 cells, thus showing two-fold selective inhibition against the oncogenic ITD mutation. The ability of 5a to modulate cell death was examined. High-throughput protein profiling revealed low levels of the growth factors IGFBP-2 and -4 with the blockage of various apoptotic inhibitors such as Survivin. p21 with cellular stress mechanisms was characterized by increased expression of HSP proteins along with TNF-β. Mechanistically, compounds 5a and 5b inhibited FLT3 kinase with IC 50 values of 2.49 and 1.45 μM, respectively. Theoretical docking studies supported