The coronavirus disease 2019 (COVID-19) pandemic, caused by the global outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has crippled public health systems and national economies globally. While vaccination campaigns are rapidly rolling out in many parts of the world, the search for safe, effective and targeted antiviral therapies that can help treat those that become infected is still ongoing.
During SARS-CoV-2’s entry into humans, the viral Spike protein (S) attaches to the human angiotensin-converting enzyme 2 (ACE2) receptor on the cell surface, which is followed by cleavage of S protein by the cellular transmembrane serine protease (TMPRSS2). The viral RNA is released into the cytosol after entry, and it highjacks host replication machinery for viral replication and assembly.
The drug targets identified for SARS-CoV-2 so far with the help of host-virus interaction studies include PLpro, 3CLpro, RNA-dependent RNA polymerase, and S proteins. Many studies on the use of natural and synthetic compounds as anti-SARS-CoV-2 drugs have reported promising results. These compounds include Pudilan Xiaoyan Oral Liquid, Tripterygium wilfordii, Saponin derivates, Glycyrrhiza glabra L., Artemisia annua, Jinhua Qinggan granules, Propolis, and Xuebijing.
A review published in Phytotherapy Research discussed the natural anti-SARS-CoV-2 products identified based on in silico prediction. The review’s authors also illustrate the impact of many phytochemicals either alone or in combination with traditional treatments and their potential molecular mechanisms involved in SARS-CoV-2 prevention and treatment.
These initial findings underscore the potential of natural compounds to be utilized as anti-SARS-CoV-2 therapeutics. However, further trial-based research, that can establish their safety and efficacy, will be crucial before any can be employed clinically.
Use of traditional Chinese medicines in the treatment of coronavirus infections
Traditional Chinese Medicines (TCM) have been used to treat previous coronavirus outbreaks and were shown to have limited side effects, shorten hospitalization time, and promote recovery from symptoms caused by the virus. Since SARS-CoV-2 is closely linked to the SARS coronavirus, researchers hypothesized that TCM used for previous outbreaks might have curative benefits that can be used to treat COVID-19. Hence, scientists developed bioinformatics tools that can predict the effectiveness of naturally occurring products and TCM in treating SARS-CoV-2 infection.
Virtual screening of the TCMD 2009 database was performed with the help of molecular docking technology and the crystal structures of PLP and Mpro. The top 100 products were selected as candidates and then classified based on the number of hit molecules. About 12,322 potential active compounds were selected as part of the Mpro inhibitors screening. The most promising among these were: aster pentapeptide A, salvianolic acid B, and ligustrazine, and Zingiberis Rhizoma Recens, Asteris Radix et Rhizoma, Notoginseng Radix et Rhizoma, Chuanxiong Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Zingiberis Rhizoma, Dianthi Herba, Rhei Radix et Rhizoma, and Cistanches Herba.
As part of the PLP inhibitor screening along with ACE2 inhibitors, many potential active components were identified. The most active photo components among these include gingerketophenol, ginkgol alcohol, ferulic acid, etc., and Codonopsis Radix, Notopterygii Rhizoma et Radix, Zingiberis Rhizoma Recens, Ginkgo Semen, Chuanxiong Rhizoma, Trichosanthis Fructus, Paeoniae Radix Alba, Psoraleae Fructus, Sophorae Flavescentis Radix, Notoginseng Radix et Rhizoma, and Angelicae Sinensis Radix.
Natural phytochemicals offer great resources for SARS-CoV-2 drug design and development
The main products that showed promise in the treatment of SARS-CoV-2 discussed in this review include Artemisia annua L., Curcuma longa, Tripterygium wilfordii, Saponin derivates, PDL, Lonicerae Japonicae Flos, XFBD, and Morus alba L., JHQGGs, and Xuebijing. However, the authors warn that these compounds may have some adverse or toxic effects at some concentrations. This needs to be further investigated to define safe doses for each of these compounds before they are to be used in any clinical setting.
The researchers emphasize:
Preliminary studies could investigate the products that have formerly been approved for drug use or are generally considered to be safe by drug regulating agencies and administrations.”
The results of this study predict 106 TCM compounds as potential drug candidates for SARS-CoV-2 treatment. The outcomes show that key meridian organs targeted by these compounds are the heart, lung, spleen, stomach, and liver meridian. These findings show that natural phytochemicals offer great resources for drug design and development. Additional chemical modulations of these compounds using computer-based docking simulations may also strengthen their effectiveness and selectivity against SARS-CoV-2.
Finally, it is hoped that the scientific community will continue to develop safe, and effective anti-SARS-CoV-2 therapeutic agents from naturally derived compounds,” write the team.