Peimine inhibits variants of SARS‐CoV‐2 cell entry via blocking the interaction between viral spike protein and ACE2

Coronavirus disease 2019 (COVID‐19) is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Several vaccines against SARS‐CoV‐2 have been approved;however, variants of concern (VOCs) can evade vaccine protection. Therefore, developing small compound drugs that directly block the interaction between the viral spike glycoprotein and ACE2 is urgently needed to provide a complementary or alternative treatment for COVID‐19 patients. We developed a viral infection assay to screen a library of approximately 126 small molecules and showed that peimine inhibits VOCs viral infections. In addition, a fluorescence resonance energy transfer (FRET) assay showed that peimine suppresses the interaction of spike and ACE2. Molecular docking analysis revealed that peimine exhibits a higher binding affinity for variant spike proteins and is able to form hydrogen bonds with N501Y in the spike protein. These results suggest that peimine, a compound isolated from Fritillaria, may be a potent inhibitor of SARS‐CoV‐2 variant infection. PRACTICAL APPLICATIONS: In this study, we identified a naturally derived compound of peimine, a major bioactive alkaloid extracted from Fritillaria, that could inhibit SARS‐CoV‐2 variants of concern (VOCs) viral infection in 293T/ACE2 and Calu‐3 lung cells. In addition, peimine blocks viral entry through interruption of spike and ACE2 interaction. Moreover, molecular docking analysis demonstrates that peimine has a higher binding affinity on N501Y in the spike protein. Furthermore, we found that Fritillaria significantly inhibits SARS‐CoV‐2 viral infection. These results suggested that peimine and Fritillaria could be a potential functional drug and food for COVID‐19 patients.

Peimine inhibits variants of SARS-CoV-2 cell entry via blocking the interaction between viral spike protein and ACE2.

Coronavirus disease 2019 (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several vaccines against SARS-CoV-2 have been approved; however, variants of concern (VOCs) can evade vaccine protection. Therefore, developing small compound drugs that directly block the interaction between the viral spike glycoprotein and ACE2 is urgently needed to provide a complementary or alternative treatment for COVID-19 patients. We developed a viral infection assay to screen a library of approximately 126 small molecules and showed that peimine inhibits VOCs viral infections. In addition, a fluorescence resonance energy transfer (FRET) assay showed that peimine suppresses the interaction of spike and ACE2. Molecular docking analysis revealed that peimine exhibits a higher binding affinity for variant spike proteins and is able to form hydrogen bonds with N501Y in the spike protein. These results suggest that peimine, a compound isolated from Fritillaria, may be a potent inhibitor of SARS-CoV-2 variant infection. PRACTICAL APPLICATIONS: In this study, we identified a naturally derived compound of peimine, a major bioactive alkaloid extracted from Fritillaria, that could inhibit SARS-CoV-2 variants of concern (VOCs) viral infection in 293T/ACE2 and Calu-3 lung cells. In addition, peimine blocks viral entry through interruption of spike and ACE2 interaction. Moreover, molecular docking analysis demonstrates that peimine has a higher binding affinity on N501Y in the spike protein. Furthermore, we found that Fritillaria significantly inhibits SARS-CoV-2 viral infection. These results suggested that peimine and Fritillaria could be a potential functional drug and food for COVID-19 patients.

Prospects of Coffee Leaf against SARS-CoV-2 Infection.

In the current climate, many countries are in dire need of effective preventive methods to curb the Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) pandemic. The purpose of this research is to screen and explore natural plant extracts that have the potential to against SARS-CoV-2 and provide alternative options for SARS-CoV-2 prevention and hand sanitizer or spray-like disinfectants. We first used Spike-ACE2 ELISA and TMPRSS2 fluorescence resonance energy transfer (FRET) assays to screen extracts from agricultural by-products from Taiwan with the potential to impede SARS-CoV-2 infection. Next, the SARS-CoV-2 pseudo-particles (Vpp) infection assay was tested to validate the effectiveness. We identified an extract from coffee leaf (Coffea Arabica), a natural plant that effectively inhibited wild-type SARS-CoV-2, and five Variants of Concern (Alpha, Beta, Gamma, Delta, and Omicron strain) from entering host cells. In an attempt to apply coffee leaf extract for hand sanitizer or spray-like disinfectants, we designed a skin-like gelatin membrane experiment. We showed that the high concentration of coffee leaf extract on the skin surface could block SARS-CoV-2 into cells more potently than 75% Ethanol, a standard disinfectant to inactivate SARS-CoV-2. Finally, LC-HRMS analysis was used to identify compounds such as caffeine, chlorogenic acid (CGA), quinic acid, and mangiferin that are associated with an anti-SARS-CoV-2 activity. Our results demonstrated that coffee leaf extract, an agricultural by-product effectively inhibits SARS-CoV-2 Vpp infection through an ACE2-dependent mechanism and may be utilized to develop products against SARS-CoV-2 infection.

Scutellaria barbata D. Don Inhibits the Main Proteases (Mpro and TMPRSS2) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection.

In late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic emerged to severely impact the global population, creating an unprecedented need for effective treatments. This study aims to investigate the potential of Scutellaria barbata D. Don (SB) as a treatment for SARS-CoV-2 infection through the inhibition of the proteases playing important functions in the infection by SARS-CoV-2. FRET assay was applied to investigate the inhibitory effects of SB on the two proteases involved in SARS-CoV-2 infection, Mpro and TMPRSS2. Additionally, to measure the potential effectiveness of SB treatment on infection inhibition, cellular models based on the Calu3 and VeroE6 cells and their TMPRSS2- expressing derivatives were assessed by viral pseudoparticles (Vpp) infection assays. The experimental approaches were conjugated with LC/MS analyses of the aqueous extracts of SB to identify the major constituent compounds, followed by a literature review to determine the potential active components of the inhibitory effects on protease activities. Our results showed that SB extracts inhibited the enzyme activities of Mpro and TMPRSS2. Furthermore, SB extracts effectively inhibited SARS-CoV-2 Vpp infection through a TMPRSS2-dependent mechanism. The aqueous extract analysis identified six major constituent compounds present in SB. Some of them have been known associated with inhibitory activities of TMPRSS2 or Mpro. Thus, SB may effectively prevent SARS-CoV-2 infection and replication through inhibiting Mpro and TMPRSS2 protease activities.