Kuwanon C for COVID-19

There has been an immense effort by global pharmaceutical companies to develop anti-COVID-19 drugs, including small molecule-based RNA replication inhibitors via drug repositioning and antibody-based spike protein blockers related to cell entry by SARS-CoV-2. However, several limitations to their clinical use have emerged in addition to a lack of progress in the development of small molecule-based cell entry inhibitors from natural products. In this study, we tested the effectiveness of kuwanon C (KC), which has mainly been researched using in silico docking simulation and can serve as an effective building block for developing anti-COVID-19 drugs, in blocking the spike S1 RBD:ACE2 receptor interaction. KC is a natural product derived from Morus alba L., commonly known as mulberry, which has known antiviral efficacy. Molecular interaction studies using competitive ELISA and the BLItz system revealed that KC targets both the spike S1 RBD and the ACE2 receptor, successfully disrupting their interaction, as supported by the in silico docking simulation. Furthermore, we established a mechanism of action by observing how KC prevents the infection of SARS-CoV-2 spike pseudotyped virus in ACE2/TPRSS2-overexpressing HEK293T cells. Finally, we demonstrated that KC inhibits clinical isolates of SARS-CoV-2 in Vero cells. Future combinations of small molecule-based cell entry inhibitors, such as KC, with the currently prescribed RNA replication inhibitors are anticipated to significantly enhance the efficacy of COVID-19 therapies.

IntroductionTraditional Chinese medicine (TCM) pharmacies in Taiwan have been a vital healthcare resource in Chinese communities, with generations of accumulated TCM knowledge playing a crucial role in infectious disease prevention and treatment. However, as proprietors age and the industry declines, this valuable ethnomedicinal knowledge faces the risk of being lost. Therefore, documenting and analyzing the knowledge used by Taiwanese TCM pharmacies in combating COVID-19 is essential for the preservation and application of ethnomedicine.MethodsThis study employed a stratified sampling method to survey 106 TCM pharmacies in Taiwan, collecting 61 TCM formulae against COVID-19. The medicinal materials were compiled, and analysis were conducted using relative frequency of citation (RFC) and the Phi correlation coefficient to examine the relationships among TCMs. Furthermore, cluster analysis was applied to establish TCM combination patterns.ResultsThis study recorded a total of 70 medicinal materials and identified 30 commonly used ones, categorizing them into four major groups: Group A (heat-clearing and detoxifying): As similar as NRICM101, suitable for moderate to severe cases. Group B (heat-clearing and tonifying): Suitable for mild cases, with both antiviral and immune-boosting effects. Group C (symptom relief): Primarily used for relieving cough, expelling phlegm, and alleviating discomfort. Group D (tonifying and strengthening): Suitable for uninfected individuals to enhance immunity.DiscussionThis study successfully documented and analyzed the TCM usage patterns of Taiwanese TCM pharmacies in combating COVID-19, revealing their alignment with modern TCM theories. The findings not only contribute to the preservation of ethnobotanical knowledge but also serve as a reference for developing herbal prevention strategies and healthcare products, ensuring that traditional medical wisdom can play a greater role within the modern healthcare system.

The ongoing COVID-19 pandemic has resulted in a global panic because of its continual evolution and recurring spikes. This serious malignancy is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the outbreak, millions of people have been affected from December 2019 till now, which has led to a great surge in finding treatments. Despite trying to handle the pandemic with the repurposing of some drugs, such as chloroquine, hydroxychloroquine, remdesivir, lopinavir, ivermectin, etc., against COVID-19, the SARS-CoV-2 virus continues its out-of-control spread. There is a dire need to identify a new regimen of natural products to combat the deadly viral disease. This article deals with the literature reports to date of natural products showing inhibitory activity towards SARS-CoV-2 through different approaches, such as in vivo, in vitro, and in silico studies. Natural compounds targeting the proteins of SARS-CoV-2—the main protease (Mpro), papain-like protease (PLpro), spike proteins, RNA-dependent RNA polymerase (RdRp), endoribonuclease, exoribonuclease, helicase, nucleocapsid, methyltransferase, adeno diphosphate (ADP) phosphatase, other nonstructural proteins, and envelope proteins—were extracted mainly from plants, and some were isolated from bacteria, algae, fungi, and a few marine organisms.