Identifying Propolis Compounds Potential to Be Covid-19 Therapies by Targeting Sars-Cov-2 Main Protease

Abstract

Objective: The study aims to perform molecular docking to examine the interaction between propolis compound and SARS-CoV-2 main protease.
 Methods: The protein target of this research was the crystal structure of SARS-CoV-2 main protease in complex with an inhibitor N3 (PDB ID: 6LU7). The ligand of this research was the bioactive compounds from Propolis of Tetragonula aff. biroi. 
 Results: The results showed that propolis compound which has the potential to inhibit SARS-CoV-2 protease activity was Sulabiroins A (binding affinity-8.1 kcal/mol), following by (2S)-5,7-dihydroxy-4'-methoxy-8-prenylflavanone acid and broussoflavonol F (binding affinity-7.9 kcal/mol) with binding similarity more than 50% compared to N3-main protease interaction.
 Conclusion: Molecular docking showed propolis compounds of Tetragonula aff. biroi potential to inhibit SARS-CoV-2 main protease activity. The highest binding affinity presented by Sulabiroins A, following by (2S)-5,7-dihydroxy-4'-methoxy-8-prenylflavanone acid and broussoflavonol F, with values of-8.1 kcal/mol,-7.9 kcal/mol, and-7.9 kcal/mol, respectively, with binding similarity more than 50% compared to N3 and SARS-CoV-2 main protease interaction.

Potential effects of propolis and honey in COVID-19 prevention and treatment: A systematic review of in silico and clinical studies

“… Khayrani et al [8] MLN-4760: –9.2 Sulabiroins A (–9.5), sulabiroins B (–8.8), 2,3-dihydro-3-hydroxypapuanic acid (–8.3), (-)-papuanic acid (–8.5), (-)-isocalolongic acid (–8.9), isopapuanic acid (–8.1), isocalopolyanic acid (–8.8), glyasperin A (–10.8), broussoflavonol F (–9.9), (2S)-5,7-dihydroxy-40-methoxy-8-prenylflavanone (–9.3), isorhamnetin (–9.2), (1S)-2-trans, 4-trans-abscisic acid (–7.3), and (1S)-2-cis, 4-trans-abscisic acid (–7.2) Glyasperin A had the highest binding affinity compared to the other 12 compounds, which was higher than MLN-4760. Main protease Dewi et al [26] Native ligand (N3): –8.4 Sulabiroins A (–8.1), sulabiroins B (–7.8), 2',3'-dihydro-3'-hydroxypapuanic acid (–7.1), (-)-papuanic acid (–7.4), (–)-isocalolongic acid (–7.2), isopapuanic acid (–7.0), isocalopolyanic acid (–6.4), glyasperin A (–7.8), broussoflavonol F (–7.9), (2S)-5,7-dihydroxy-4'-methoxy-8-prenylflavanone (–7.9), isorhamnetinb (–7.3), (1'S)-2-trans,4-trans-abscisic acid (–6.5), (1'S)-2-cis,4-trans-abscisic acid (–6.0), curcumene (–5.5), thymol (–4.7), tetralin (–4.7), P-coumaric acid (–5.1), α-tocopherol succinate (–6.2), deoksi podophyllotoxin (–7.4), and xanthoxyletin (–6.7) Sulabiroins A had the highest binding affinity compared to the other 19 compounds, which was lower than native ligand (N3). Elwakil et al [16] Lopinavir: –8.18 Acid: n-hexadecanoic acid (–6.28), benzoic acid (–3.70), trans-caffeic acid (–4.48), tetradecanoic acid (–5.84), and trans-13-octadecenoic acid (–6.06) Octacosanol showed the highest binding affinity compared to the other 25 compounds, which was lower than lopinavir.…”

“…A total of six in silico studies were conducted using the SARS-CoV-2 main protease enzyme as the target enzyme [16,25 − 29]. Several compounds from propolis had high binding affinity to the SARS-CoV-2 main protease enzyme, including octacosane ( − 7.39 kcal/mol) [16] , 3′-methoxydaidzin ( − 7.7 kcal/mol) [25] , sulabiroins A ( − 8.1 kcal/mol) [26] , rutin ( − 92.8 kcal/mol) [27] , glyasperin A ( − 7.8 kcal/mol) [28] , broussoflavonol F ( − 7.8 kcal/mol) [28] , and kaempferol ( − 7.8 kcal/mol) [29] ( Table 2 ).…”

Identification of Potential Activity of Volatile Compounds Derived From Pogostemon Cablin Benth as Antiviral of Sars-Cov-2

“…Furthermore, protein structure was added by hydrogen polar as preparation for further analysis. The MLN-4760 and sulabiroins A were selected as control for the analysis [8].…”

Antiviral, Antibacterial, Antifungal, and Antiparasitic Properties of Propolis: A Review

“…Refaat et al (2021) demonstrated that propolis delivered in a liposomal encapsulation was as effective as remdesivir in neutralizing SARS-CoV-2 in vitro [90]. Many computational and molecular docking studies suggest the efficacy of propolis and its phenolic components in interfering with many important proteins of the SARS-CoV-2, including proteases and the spike protein [91][92][93][94].…”

“…Caffeic acid phenethyl ester was also shown to interfere with the highly conserved residues (substrate-binding pocket) of M pro protein of SARS-Cov-2 [113]. In addition, molecular docking studies by Sahlan et al (2021) and Dewi et al (2021) demonstrated that Sulabiroins A, (2S)-5,7-dihydroxy-4 -methoxy-8-prenylflavanone acid, glyasperin A, and broussoflavonol F (propolis-derived compounds) could potentially bind to various residues of M pro catalytic sites and consequently inhibit the activity of the M pro protein of SARS-Cov-2 [93,94]. Kwon et al (2020) demonstrated that kaempferol and p-coumaric acid prevented the entry of human rhinovirus and also inhibited the viral replication in HeLa cells [112].…”