Luteolin: a blocker of SARS-CoV-2 cell entry based on relaxed complex scheme, molecular dynamics simulation, and metadynamics

Abstract

Natural products have served human life as medications for centuries. During the outbreak of COVID-19, a number of naturally derived compounds and extracts have been tested or used as potential remedies against COVID-19. Tetradenia riparia extract is one of the plant extracts that have been deployed and claimed to manage and control COVID-19 by some communities in Tanzania and other African countries. The active compounds isolated from T. riparia are known to possess various biological properties including antimalarial and antiviral. However, the underlying mechanism of the active compounds against SARS-CoV-2 remains unknown. Results in the present work have been interpreted from the view point of computational methods including molecular dynamics, free energy methods, and metadynamics to establish the related mechanism of action. Among the constituents of T. riparia studied, luteolin inhibited viral cell entry and was thermodynamically stable. The title compound exhibit residence time and unbinding kinetics of 68.86 ms and 0.014 /ms, respectively. The findings suggest that luteolin could be potent blocker of SARS-CoV-2 cell entry. The study shades lights towards identification of bioactive constituents from T. riparia against COVID-19, and thus bioassay can be carried out to further validate such observations. Supplementary Information The online version contains supplementary material available at 10.1007/s00894-021-04833-x.

Analysis and Identification of Bioactive Compounds of Cannabinoids in Silico for Inhibition of SARS-CoV-2 and SARS-CoV

“…Furthermore, our results revealed that CBNA could bind to Tyr453 of SARS-CoV-2 RBD-ACE2, consistent with the binding between luteolin and ACE2 [ 16 ]. This indicates that CBNA and luteolin all have the potential ability to block viral recognition and entry.…”

“…When luteolin was targeted at RdRP by molecular docking, and its docking score was −7.62 kcal/mol [ 15 ], it suggested there were differences in inhibition of SARS-CoV-2 even when the same bioactive molecule was targeted on different proteins. The binding energy of luteolin-inhibited cell entry was −36.82 kJ/mol [ 16 ], while CBDA was −6.3 kcal/mol [ 17 ].…”

“…Several natural substances, including bee product alkaloids, terpenoids, marine products, and other natural products, have been confirmed as potential inhibitors against COVID-19 for targeting M pro , RdRp and Nsp of SARS-CoV-2 [ 12 , 13 , 14 , 15 ]. In addition, several natural products have been found that can block SARS-CoV-2 cell entry, including luteolin and CBDA [ 16 , 17 ]. Cannabis has recently been proposed as a potential COVID-19 inhibitor based on the bioactive substances it contains, such as CBD and THC [ 18 ].…”

In Silico Approach for the Evaluation of the Potential Antiviral Activity of Extra Virgin Olive Oil (EVOO) Bioactive Constituents Oleuropein and Oleocanthal on Spike Therapeutic Drug Target of SARS-CoV-2

“…Two hydrophobic contacts of (S)-Linezolid with ACE2 were also found to be common with those of OC, namely Asn N33 and Pro P389. Furthermore, binding contacts N33, H34, D38, Y453, and P389 (with the latter playing a critical role in the interaction of both OEU and OC on ACE2), were revealed to be in common with luteolin [ 99 , 100 ]; N33, H34, and P389 were in common with andrographolide; H34, A387, and P389 were in common with artemisinin; and H34 was in common with pterostilbene [ 26 ], bound at the same RBD/ACE2 interface.…”

Effectivity of repurposed drugs against SARS-CoV-2 infections, A hope for COVID 19: inhibitor modelling studies by docking and molecular dynamics

“…All of the above-mentioned individual antiviral and antibiotic drugs have been tested for the prevention and effective management of COVID-19 infection. Till now the available clinical data validated that most of the repurposed drugs tested for COVID-19 treatment, have shown lower or moderate effectiveness with many adverse side effects for the patient conditions like diabetes, hypertension, cardiac problems 19 , 20 . Many repurposed combination drugs have also repositioned for the treatment of HIV, other coronaviruses and MERS-CoV infection [ 21 ].…”