Hesperidin Is a Potential Inhibitor against SARS-CoV-2 Infection.

Fang-Ju Cheng,Chia-Shin Yang,Dai-Wei Hu,Yi-Cheng Shen,Wei-Chien Huang,Yeh Chen,Chih-Yen Tu,Yang-Chang Wu,Thanh-Kieu Huynh,Chien-Yi Ho,Chih-Hsin Tang

doi:10.3390/nu13082800

Abstract

Hesperidin (HD) is a common flavanone glycoside isolated from citrus fruits and possesses great potential for cardiovascular protection. Hesperetin (HT) is an aglycone metabolite of HD with high bioavailability. Through the docking simulation, HD and HT have shown their potential to bind to two cellular proteins: transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2), which are required for the cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our results further found that HT and HD suppressed the infection of VeroE6 cells using lentiviral-based pseudo-particles with wild types and variants of SARS-CoV-2 with spike (S) proteins, by blocking the interaction between the S protein and cellular receptor ACE2 and reducing ACE2 and TMPRSS2 expression. In summary, hesperidin is a potential TMPRSS2 inhibitor for the reduction of the SARS-CoV-2 infection.

Highlights

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a single-stranded and positive-sense RNA virus in the betacoronavirus family, caused the global pandemic of coronavirus disease in 2019 (COVID-19) [1,2]
The results showed that angiotensin-converting enzyme2 (ACE2) (Figure 1A–F) and TMPRSS2 (Figure 1G–L), the cellular proteins involved in the entry of SARS-CoV2, could interact with HT and HD, and that the energy values of ACE2-HT, ACE2-HD, TMPRSS2-HT, and TMPRSS2-HD were −34.81, −1.65, −30.56, and −7.2 kCal/mol, respectively (Table 1)
These two compounds yielded an interaction with papain-like protease (PLpro) (Figure 2A–F) and 3-chymotrypsin-like protease (3CLpro) (Figure 2G–L), the viral proteins involved in the replication of SARS-CoV2

Summary

Introduction

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a single-stranded and positive-sense RNA virus in the betacoronavirus family, caused the global pandemic of coronavirus disease in 2019 (COVID-19) [1,2]. The cell entry of SARS-CoV-2 depends on the binding of the viral spike (S) protein to the cellular receptor angiotensin-converting enzyme (ACE2). Through the binding between the S1 subunit and ACE2, the S protein is cleaved into the domains of S1 and S2 by host transmembrane serine protease 2 (TMPRSS2) to expose the fusion peptide on S2 for the subsequent membrane fusion and cellular entry of viral RNA [4,5]. For the development of preventive or therapeutic approaches against SARS-CoV-2 infection, the critical proteins involved in the cellular attachment and replication of SARS-CoV-2 are considered as effective targets [5,8,9,10]

Methods

Results

Conclusion