Mulberrofuran G, a Mulberry Component, Prevents SARS-CoV-2 Infection by Blocking the Interaction between SARS-CoV-2 Spike Protein S1 Receptor-Binding Domain and Human Angiotensin-Converting Enzyme 2 Receptor

Abstract

Despite the recent development of RNA replication-targeted COVID-19 drugs by global pharmaceutical companies, their prescription in clinical practice is limited by certain factors, including drug interaction, reproductive toxicity, and drug resistance. COVID-19 drugs with multiple targets for the SARS-CoV-2 life cycle may lead to a successful reduction in drug resistance as well as enhanced therapeutic efficacy, and natural products are a potential source of molecules with therapeutic effects against COVID-19. In this study, we investigated the inhibitory efficacy of mulberrofuran G (MG), a component of Morus alba L., also known as mulberry, which has been used as food and traditional medicine, on the binding of the spike S1 receptor-binding domain (RBD) protein to the angiotensin-converting enzyme 2 (ACE2) receptor, which is the initial stage of the SARS-CoV-2 infection. In competitive enzyme-linked immunosorbent assays, MG effectively blocked the spike S1 RBD: ACE2 receptor molecular binding, and investigations using the BLItz system and in silico modeling revealed that MG has high affinity for both proteins. Finally, we confirmed that MG inhibits the entry of SARS-CoV-2 spike pseudotyped virus and a clinical isolate of SARS-CoV-2 into cells, suggesting that MG might be a promising therapeutic candidate for preventing SARS-CoV-2 binding to the cell surface during early infection.

Structurally Diverse Stilbenoids as Potent α-Glucosidase Inhibitors with Antidiabetic Effect from Morus alba

“…It was worth noting that mulberrofuran G ( 6 ) had been reported a lot from different Morus species since its first isolation from M. alba, and it exerted diverse biological properties including cyclic AMP phosphodiesterase inhibitory, antibacterial, cytotoxic, , tyrosinase inhibitory, antiviral, , cytoprotective, , protein tyrosine phosphatase 1B, and tyrosinase inhibitory activities, as well as inhibition against multiple targets of Alzheimer’s disease. , Also, it was reported to show potent α-glucosidase inhibitory effect . However, all of these previous biological tests were only conducted in vitro at molecular and cellular levels, with no in vivo evaluation recorded so far.…”

A Comprehensive Update of Various Attempts by Medicinal Chemists to Combat COVID-19 through Natural Products

“…In vitro studies showed that this natural compound inhibited the SARS-CoV-2 infection by interacting with both the viral spike proteins and the host ACE2 receptor cells with an IC 50 of 10.23 μM at a concentration of less than 50 μM. Furthermore, in silico studies demonstrated the more stable binding interactions of ligands with spike proteins compared to ACE2 receptors [ 63 ] ( Table 1 ).…”

Biobran/MGN-3, an Arabinoxylan Rice Bran, Exerts Anti-COVID-19 Effects and Boosts Immunity in Human Subjects

“…Therefore, it is worthwhile to investigate the potential of certain biological response modifiers (BRMs) to boost the antiviral immune response and lower hospitalization risk. There have been earlier studies over an extensive range of natural products, herbal supplements, and traditional medicine products that have been reported to work against COVID-19 in vitro [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. However, we are not aware of an in vivo human study that was carried out showing the efficiency of a food supplement in exerting anti-COVID-19 effects, though vitamin C has been shown to shorten patient stays in intensive care units by 8.6% [ 29 ] and to shorten the period under mechanical ventilation by 18.2% [ 30 ].…”