Traditional medicine has been used for centuries to ward off diseases and pathogens. With the vast spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen responsible for the coronavirus disease 2019 (COVID-19), scientists are still racing to find effective compounds that can be used to develop drugs to treat this infection.
Over the past year, numerous studies have tried to find in silico evidence to determine whether certain natural compounds might be effective against SARS-CoV-2. More recently, a group of researchers at Kannur University in Thalassery, India led by Dr. Janaki Ammal Campus reviewed selected papers and in silico work on potential drug leads that could be used to manage COVID-19. Their study, which was published in the Future Journal of Pharmaceutical Sciences, identified phytochemicals as the leading compounds that could be used to develop antiviral drugs against SARS-CoV-2.
Study: Potent phytochemicals against COVID-19 infection from phyto-materials used as antivirals in complementary medicines: a review. Image Credit: Tatajana Baibakova / Shutterstock.com
The COVID-19 pandemic
The COVID-19 pandemic first emerged in December 2019 in Wuhan, China. From there, SARS-CoV-2 continued to spread to 192 countries and regions. As of June 14, 2011, over 175 million people have been diagnosed with COVID-19, of which almost 3.8 million people have died as a result of this disease.
This global health crisis has taken a toll on many countries, both economically and socially, with many business closures and a ban on social gatherings.
SARS-CoV-2 can cause a wide range of symptoms, with the infection severity often being determined by the affected population, such as the elderly and those with comorbidities. Currently, several effective vaccines have been developed and approved to mitigate the risk of infection by SARS-CoV-2. As a result, many countries around the world have started vaccination rollouts in an effort to attain herd immunity.
SARS-CoV-2 is a coronavirus that shares a 79% structural similarity with the severe acute respiratory syndrome coronavirus (SARS-CoV), which was the virus behind the severe acute respiratory syndrome (SARS) outbreak in 2002. This structural similarity is also evident between SARS-CoV-2 and the Middle East respiratory syndrome coronavirus (MERS-CoV), which was the virus responsible for the 2012 outbreak in Saudi Arabia.
The central antigenic part of the SARS-CoV-2 is the spike (S) protein, which is a highly glycosylated and large transmembrane fusion protein. Unlike the other functional proteins of SARS-CoV-2, the S protein is responsible for inducing the host immune response. Therefore, neutralizing antibodies that target the S protein can often induce protective immunity against viral infection.
In addition to studies evaluating the efficacy of vaccines in preventing the spread of COVID-19, several scientists are also focusing on repurposing currently approved drugs to treat this disease. Though several different drugs have proven useful in treating COVID-19, many of them are associated with adverse effects. Therefore, finding drugs that have fewer side effects, such as herbal preparations, is still warranted.
Phytochemicals for COVID-19
Since ancient times, people have depended on naturally available materials like phytochemicals, which include herbal extracts, concoctions, or decoctions. Phytochemicals with enhanced bioactivity and reduced toxicity may be effective alternatives to treat diseases like COVID-19.
Some of the major phytochemicals include flavonoids, terpenoids, alkaloids, and phenolic and essential oils. One example of a widely used phytochemical is quinine, an alkaloid from the cinchona tree bark used to treat malaria and other infectious diseases like pneumonia, typhoid fever, and nasopharyngeal infections.
Several previous studies have confirmed the efficacy of phenolic subclasses like flavonoids, phenolic acids, coumarins, tannins, and stilbenes in the treatment of viral infections like the Zika virus, influenza, chikungunya virus, dengue virus, rotavirus, Japanese encephalitis virus, herpes, hepatitis, human papillomavirus (HPV), and the human immunodeficiency virus (HIV).
The current review describes the utility of comprehensive molecular docking studies (MDS) analyses to evaluate promising drug leads for the treatment of COVID-19. Incorporating in silico work into these analyses can help provide meaningful results on the potential efficacy of these drugs for this indication.
In their work, the researchers identified several phytochemicals that could be repurposed for treating SARS-CoV-2. Stilbene-based natural compounds, for example, are potent inhibitors of the complex that arises following the binding of the SARS-CoV-2 S protein with the angiotensin-converting enzyme 2 (ACE2) receptor on host cells. Essential oils like carvacrol, cinnamaldehyde, cinnamyl acetate, geraniol, L-4-terpineol, and anethole were also found to exhibit improved binding affinity towards the S protein through their interaction with ACE2. In fact, the essential oil component of garlic showed potent inhibitory effects against ACE2.
Several traditional medicines were also investigated for their potential utility in treating SARS-CoV-2. Ayurvedic medications, which are traditional Indian herbs that have been historically used for treating various ailments, have also been used for their antiviral properties. Gingseng, for example, has demonstrated in silico inhibitory effects against SARS-CoV-2.
Siddha, which is another traditional type of medicine that has been historically used in India, also offers several distinct herbal formulations that have been used to treat a wide range of illnesses. This system of medications includes quercetin, luteolin, and chrysoeriol, all of which have demonstrated a unique binding affinity with the receptor-binding domain (RBD) of SARS-CoV-2. The RBD domain of this virus is believed to play a critical role in the attachment and fusion between the S protein of SARS-CoV-2 and the host cell.
Different preparations from Traditional Chinese Medicine have not only been evaluated for their use in treating COVID-19 but were also widely studied during the previous SARS outbreak of 2003. Shufeng Jiedu capsules, Lianhua Qingwen capsules, and Jinhua Qinggan granules, for example, have all been used for treating the fatigue and fever symptoms associated with COVID-19.
Taken together, the authors of the current review assessed studies published on alternative remedies that could be used to treat COVID-19. In their work, the researchers found that there are, in fact, many potential drug lead compounds in traditional medicines that can be used for treating SARS-CoV-2 infection or similar infections.
The team also noted that one of the most interesting findings that they came across was that linoleic acid can efficiently bind onto the SARS-CoV-2 spike protein, thereby demonstrating the strong possibility of viral inhibition by this compound. This suggests that free fatty acids or their derivatives may play an imperative role in the drug discovery process for COVID-19.
“MDS analyses may be considered together with the application of other in silico methods of prediction of pharmacological properties directing towards the sites of drug-receptor regulation. Also, the present analysis would help formulate new recipes for complementary medicines."