In silico study on spice-derived antiviral phytochemicals against SARS-CoV-2 TMPRSS2 target

Experimental and clinical evidence on the effect of carvacrol on respiratory, allergic, and immunologic disorders: A comprehensive review

“…CAR also increased viral titer compared to the RSV‐PBS group, 62 but decreased levels of TLR7, MyD88, NF‐κB, and IRF mRNA in virus infected model 63 . The molecular dynamic simulation studies indicated that molecular interactions between CAR and spike protein of SARS‐CoV‐2 together with the cellular proteases TMPRSS2, showed that the CAR could inhibit the entry of the virus to the host cells 65,67 …”

“…66 Molecular dynamic simulation (MDS) analysis showed CAR and thymol as better inhibitors than the camostat (a well-known synthetic inhibitor of TMPRSS2) due to their stable binding 32 with TMPRSS2 in its oxyanion hole. 67 The results of a study suggest that the CAR could serve as potential inhibitor in regulating the main protease (M pro ) of COVID-19 function and controlling viral replication. 68 In a viral infection mice model, treatment CAR at a volume of 0.2 ml for 5 days, lung pathological changes and the expression levels of cytokines were assessed.…”

Host Cell Proteases Mediating SARS-CoV-2 Entry: An Overview

“…Homology modeling QM/MM-MD Structural analysis of TMPRSS2 bonding with Camostat and its metabolite GBPA [49] Homology modeling QM/MM-MD Structural analysis of TMPRSS2 bonding with Nafamostat +Camostat and its metabolite GBPA [47] Homology modeling + Pharmacophore + Docking + MD Four non-covalent inhibitors (Otamixaban, UK-1, NCGC00386945, and NCGC00487181) against TMPRSS2 are still less effective than camostat and nafamostat [50] Homology Modeling + MD Non-target binding study of nafamostat and camostat [51] MD MD analysis of binding nafamostat, camostat, gabexate, Bromhexine [52] Homology modeling + Virtual screening + Docking 156 small molecules proposed to have an excellent inhibition profile against TMPRSS2 [53] Homology modeling + Docking + MD Allosteric binding site BH [48] Homology modeling + Docking + MD Three phytochemicals (Niazirin, Quercetin, and Moringyne) are better than camostat [54] Homology modeling + Docking + MD Cepharanthine is better than camostat [55] Homology Homology modeling + Docking + MD bisdemethoxycurcumin (BDMC), carvacrol, and thymol have better inhibition than camostat [62] Homology modeling + Docking + MD Robinin, Daidzin, and Hydroxytuberosonehave potential inhibition profile against TMPRSS2 [63] Homology modeling + Docking + MD structural analysis of TMPRSS bonding with camo + nafamostat+ bromhexine [64] Homology moeling + Docking + MD Structural analysis of TMPRSS2 binding with nafa+camostat+gabexate +sivelestat [65] Homology modeling + Docking + MD 5 phytochemicals against TMPRSS2 [66] Homology modeling + Docking + MD Withaferin A + Withanolide D has a dual inhibition profile targeting TMPRSS2 and ACE2 [67] Docking + MD Ibrutinib and zanubrutinib may have multiple inhibition profiles against TMPRSS and viral proteins [68] Homology modeling + Docking + MD Withanone and Withaferin A may have a better inhibition profile than camostat [69] Homology modeling + Docking + MD benzquercin proposed as a robust TMPRSS2 inhibitor [70] Homology modeling + Docking + MD Leupeptin may be a good alternative for camostat [71] H, K, L, O, S, V, W, and X) [84]. Among all cathepsins, an abundance of cathepsin B and L is noticed [85].…”

Nigella sativa L. Phytochemistry and Pharmacological Activities: A Review (2019–2021)

“…The inhibitory power of several bioactive compounds was tested in silico on transmembrane serine protease 2 (TMPRSS2) which is an enzyme present at the level of pneumocytes II and in the case of the presence of the virus this enzyme truncates (amputates) the spike protein which thus facilitates its endocytosis. The results obtained show that carvacrol was able to theoretically inhibit TMPRSS2 more than Comstat used as a control, while thymol, given in silico, always produced a low activity [ 65 ]. A study conducted by Sajjad Ahmad et al, showed that nigellone, also called dithymoquinone, was able to theoretically inhibit all four crucial targets of coronavirus [ 66 ], while nigellidine and kaempferol, which are two compounds present at the seed level, also showed a high affinity with COVID-19 C19MP proteases [ 67 ] ( Table 2 ).…”