PLANT MOLECULES AS POTENTIAL ANTIVIRAL DRUGS AGAINST COVID-19
Dr. Abraham Peele
Collated by Dr. Divyashree C. Nageswaran
Viral infections are reported to affect ~3-5 million people a year. The infections range from a mild common cold to deadly one like COVID-19, intimidating people’s health and even their lives. Although vaccines have been controlling many viral diseases, anti-viral drugs may help in tackling some highly infectious diseases. In the recent times, there has been a significant progress witnessed on the development of novel anti-viral drugs. Newly developed drugs majorly fall into three groups, Nucleotide analogues, nucleoside analogues and some special inhibitors of viral enzymes. Most FDA-approved drugs are nucleotide analogues that include, Favipiravir, Remdesivir, Ribavarin and Galidesivir, have been considered to target viruses, including SARS-CoV-2 by acting as RNA-dependent RNA polymerase (RdRp) inhibitors, where the enzyme mediates viral replication. Other possible drugs like Saquinavir, Tipranavir, Lonafarnib, Tegobuvir, Filibuvir, Cepharanthine and Olysio have been identified to possess antiviral activity, and in silico predictions suggest that they are potential inhibitors of RdRp activity. In addition, the main protease called 3-chymotrypsin-like protease (3CL_protease) are targeted to inhibit replication as they are important for cleaving polyproteins into RdRp and other replication-involved proteins. Hence, FDA- approved drugs of HIV protease inhibitors, including Indinavir, Amprenavir, Atazanavir, Darunavir, Lopinavir, Ritonavir, Nelfinavir and few more along with nucleotide analogues like Remdesivir were computationally analysed. However, in vitro testing and clinical trials are absolutely mandatory to prove that the potential drug molecules help in treating COVID- 19.
Phytochemicals, on the other hand, could serve as an alternative source of treatment and cure owing to their non-toxicity, low-cost, minimal side-effects and most of all potential antiviral properties. Globally, around 2500 medicinal plant species have been identified to treat many infectious diseases. A vast repository of bioactive components, including alkaloids, terpenes, flavonoids, polyphenols, quinones, saponins, proanthocyanidins, steroids, lignins, thiosulfonates, tannins, polysaccharides and coumarines have been identified to combat several viral infections. Traditional Ayurveda and Chinese medicines that uses various medicinal plant metabolites have shown to have potent antiviral activities. Hence, it is important to investigate on such medicines as well for its potential to emerge as novel antiviral agents against viral infections, including the current pandemic.
Numerous screening studies have been conducted until today so as to identify the antiviral potentials of plants and their specific parts (e.g. leaf), and also test for antiviral efficacy through in vitro and in vivo tests. For example, two plant compounds, namely; glycyrrhizin and lycorine were isolated from Glycyrrhiza uralensis and Lycoris radiata, respectively showed strong antiviral activity against the RNA virus, SARS-CoV, which caused the pandemic years before the current one. Likewise, previous works also propose that natural compounds have a broad-spectrum of antiviral properties against RNA viruses, including specific types of poliovirus, parainfluenza virus, and respiratory syncytial virus by curtailing its replication process. In this context, virtual screening of phytochemicals are conducted for its inhibitory mode of action against the main protease, structural (e.g. spike protein) and non-structural proteins (e.g. NSP12 encoding RdRp) of RNA viruses, including the beta-CoV, SARS-CoV-2. Such in silico methods have predicted plant antiviral compounds like polyphenols, flavonoids and other natural products that can act against SARS-CoV-2. Indeed, it is essential to carry out in vitro and in vivo randomized clinical trials to launch prospective drug molecules from plant sources as the primary lead in blocking replication.
In addition to that, nutritive phytochemicals may prove beneficial in stimulating a good immune response against the COVID-19 condition. Immune responses that are induced by the later stages of viral infection are called the “cytokine storm”. They are basically associated with excessive levels of pro-inflammatory cytokines and widespread tissue damage. In this case, phytochemicals may help in initiating an immune response in the early stages to reduce the risk of the infection progressing further up to the occurrence of a cytokine storm. For example, Curcumin is a phytochemical component of turmeric controls the expression of cytokines, transcription factors (e.g. PPAR-gamma), enzymes and adhesion molecules that contribute to inflammation. With its anti-inflammatory effect catalyses PPAR-gamma activation, which blocks the cytokine TNF-alpha that is responsible for inflammation. Hence, these natural and nutritive compounds can be a therapeutic option to prevent inflammatory effects after the occurrence of CoV infections.