Molecular interaction analysis of Sulawesi propolis compounds with SARS-CoV-2 main protease as preliminary study for COVID-19 drug discovery

Abstract

Coronavirus disease 2019 (COVID-19), a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health concern, as the World Health Organization declared this outbreak to be a global pandemic in March 2020. The need for an effective treatment is urgent because the development of an effective vaccine may take years given the complexity of the virus and its rapid mutation. One promising treatment target for COVID-19 is SARS-CoV-2 main protease. Thus, this study was aimed to examine whether Sulawesi propolis compounds produced by Tetragonula sapiens inhibit the enzymatic activity of SARS-CoV-2 main protease. In this study, molecular docking was performed to analyze the interaction profiles of propolis compounds with SARS-CoV-2 main protease. The results illustrated that two compounds, namely glyasperin A and broussoflavonol F, are potential drug candidates for COVID-19 based on their binding affinity of −7.8 kcal/mol and their ability to interact with His 41 and Cys 145 as catalytic sites. Both compounds also displayed favorable interaction profiles with SARS-CoV-2 main protease with binding similarities compared to inhibitor 13b as positive control 63% and 75% respectively.

Current Updates on Naturally Occurring Compounds Recognizing SARS-CoV-2 Druggable Targets

“…In-silico study reported that broussoflavonol F ( Figure 17 a) could better recognize SARS-CoV-2 Mpro active site due to the interaction with the catalytic dyad Cys145 and His41 [ 137 ].…”

Fighting against the second wave of COVID-19: Can honeybee products help protect against the pandemic?

“…On the other hand, very few studies investigated the potential effects of propolis on coronaviruses ( Bachevski et al, 2020a , Debiaggi et al, 1990 ). Propolis is rich in phenolics and flavonoids (see Table 2 ) , several in vitro and in silico studies confirmed anti‐coronavirus activity of propolis flavonoids like chrysin and kaempferol that were found to inhibit virus replication in vitro ( Debiaggi et al, 1990 ) and quercetin and its derivatives that inhibit the SARS‐CoV‐1 and MERS‐CoV main protease in vitro besides their aminopeptidase activity and their ability to modulate the unfolded protein response (UPR) utilized by the virus to complete the replication cycle ( Bachevski et al, 2020b , Berretta et al, 2020 , Polansky and Lori, 2020 , Sahlan et al, 2020 , Scorza et al, 2020 , Shaldam, n.d. , Syed and Saleem, 2004 ). Taken together and based on recent and previous findings about propolis immunomodulator and antiviral activity, it could be used as adjuvant therapy to control the severe inflammatory reaction especially the cytokine storm associated with COVID-19 infection aside from the protective effects of propolis phenolics and flavonoids against COVID-19.…”

Propolis, Bee Honey, and Their Components Protect against Coronavirus Disease 2019 (COVID-19): A Review of In Silico, In Vitro, and Clinical Studies

“…Molecular modeling and computational approaches—which predict the conformation of the ligand within the receptor and quantify the affinity of binding as a docking score (kcal/mol)—may allow a rapid and relatively cheap evaluation of the effectiveness of numerous compounds [ 5 , 42 ]. Given the documented antiviral, anti-inflammatory, antioxidant, and immunomodulatory activities of various bee products [ 19 , 31 , 33 , 43 , 44 ], we searched PubMed and Google Scholar for studies investigating their anti-COVID-19 effects using a combination of terms “propolis, bee honey, royal jelly, bee venom, bee pollen, phenolic compounds, flavonoids, coronavirus, SARS-CoV-2, COVID-19, in vitro, and randomized clinical trials.” Studies using active compounds in propolis and bee honey to target SARS-CoV-2 activities in silico, in vitro, and in humans were used for the synthesis of this narrative review.…”

“…Kaempferol and p -coumaric acid remarkably reduced the RNA replication levels when administered early within 0–4 h after virus inoculation [ 58 ]. Propolis exerts a viricidal activity by destroying viral outer envelope (e.g., of human immunodeficiency virus); it also inhibits viral replication and transmission among cells [ 42 ]. Flavonoids of propolis are reported to exhibit potent ACE-inhibiting properties in vivo and in vitro [ 49 , 56 ].…”

“…Given that alterations in NSPs such as 3CLpro/Mpro, PLpro, and RdRp interfere with viral replication and threaten viral survival [ 1 , 47 , 87 ], several studies have examined the interaction of flavonoids in propolis and honey with these key viral enzymes [ 25 , 42 , 47 , 51 , 86 ]. Preliminary results pinpoint an inhibitory activity of flavonoids against NSPs of SARS-CoV-2 [ 25 , 42 , 47 , 51 ]. The binding affinity of luteolin (−8.2 kcal/mol) to Mpro/3CLpro is reported to be greater than that of hydroxychloroquine, remdesivir, and Camostat mesylate (−5.4, −6.5, and −5.9 kcal/mol, respectively ( Figure 3 c) [ 86 ].…”