Kuwanons, Promising inhibitors against the ACE-2, main protease of SARS-CoV-2 and falcipan-2 using molecular docking

Abstract

In the present scenario, the COVID-19 has affected the nations throughout the world. Till date, neither a vaccine nor a potential medicine is available for the cure from SARS-CoV-2 infection. Main protease of SARS-CoV-2 is responsible for the replication and transcription. Further, this virus binds to the angiotensin converting enzyme-2 (ACE-2) so there is need to find molecule, to avoid the binding of novel virus to ACE-2. It is reported that the molecules binds to falcipan-2 can help in the reduction of infection due to SARS-CoV-2. Therefore, there is a need to find promising candidate against the receptors, spread COVID-19. In the present work, kuwanons are proposed to be promising candidates against the main protease of SARS-CoV-2, ACE-2 and falcipan-2. The interaction between the different kuwanons with different receptors has been studied using the binding energy. Kuwanon M was found to best inhibitor against the main protease of SARS-CoV-2 and ACE-2. Further, the drug-likeness properties of all the 16 kuwanons were studied. Kuwanon-M found to be best inhibitor against the ACE-2 and main protease of SARS-CoV-2 with binding energy of -165.349 and -149.952 kcal/mol respectively while kuwanon-G found out to promising against the falcipan-2 with a binding energy of -149.573 kcal/mol.

Mulberry Component Kuwanon C Exerts Potent Therapeutic Efficacy In Vitro against COVID-19 by Blocking the SARS-CoV-2 Spike S1 RBD:ACE2 Receptor Interaction

“…We then investigated the binding affinity of KC for the spike S1 RBD and the ACE2 receptor using the BLItz system, and found that KC had equilibrium dissociation constants ( K D ) of 5.03 × 10 −4 M for the spike S1 RBD and 8.11 × 10 −4 M for the ACE2 receptor ( Figure 2 and Table 1 ). Collectively, most of the natural product-derived inhibitors targeting the spike S1 RBD:ACE2 receptor interaction have been investigated based on in silico simulation [ 29 , 39 , 40 , 41 , 42 , 43 ]; however, this study not only provides information on a building block of COVID-19 therapeutic agents with the MoA that inhibits SARS-CoV-2 cell entry based on the actual molecular interaction between KC and the spike S1 RBD/ACE2 receptor, it also suggests that further structural analysis of KC derivatives is warranted to obtain increased binding affinity for both proteins.…”

“…A previous report showed the binding energy of KC for the ACE2 receptor, the main protease of SARS-CoV-2, and falcipan-2; however, comprehensive research on the molecular interactions of KC is required [ 29 ]. Thus, we predicted the binding mode of KC to both the spike protein and ACE2 receptor using in silico binding simulation, as well as the molecular interactions between KC and amino acid residues of each protein in that mode using pharmacophore analysis.…”

“…Therefore, future study on KC in vivo should closely monitor RAS regulation and cancer prognosis, which may be caused by KC binding to the ACE2 receptor. In addition, Kumari et al suggested that KC may act as an inhibitor for the main protease of SARS-CoV-2 and falcipain-2 involved in SARS-CoV-2 replication as well as ACE2 receptor binding through in silico molecular docking analysis [ 29 ], indicating that KC may be effective against COVID-19 by blocking SARS-CoV-2 entry via ACE2 receptor binding and inhibiting SARS-CoV-2 replication. However, since the prediction based on in silico analysis does not necessarily correlate with actual experimental results, it is required to examine the anti-COVID-19 efficacy of KC via other antiviral mechanisms using the suitable cell lines and KC treatment method.…”

“…KC has been reported to have a variety of biological activities, such as antiviral, antibacterial, antifungal, tyrosinase inhibitory, antioxidant, neuroprotective, and anti-inflammatory effects [ 19 , 23 , 24 , 25 , 26 , 27 , 28 ]. For COVID-19, KC has only been investigated in an in silico docking study with the ACE2 receptor [ 29 ]; no in vitro studies of efficacy for preventing clinically isolated SARS-CoV-2 infection by blocking the spike S1 RBD:ACE2 receptor interaction have been performed.…”