Withaferin A: a potential therapeutic agent against COVID-19 infection

Abstract

The outbreak and continued spread of the novel coronavirus disease 2019 (COVID-19) is a preeminent global health threat that has resulted in the infection of over 6 million people worldwide. In addition, the pandemic has claimed the lives of over 350,000 people worldwide. Age and the presence of underlying comorbid conditions have been found to be key determinants of patient mortality. One such comorbidity is the presence of an oncological malignancy, with cancer patients exhibiting an approximate two-fold increase in mortality rate. Due to a lack of data, no consensus has been reached about the best practices for the diagnosis and treatment of cancer patients. Interestingly, two independent research groups have discovered that Withaferin A (WFA), a steroidal lactone with anti-inflammatory and anti-tumorigenic properties, may bind to the viral spike (S-) protein of SARS-CoV-2. Further, preliminary data from our research group has demonstrated that WFA does not alter expression of ACE2 in the lungs of tumor-bearing female mice. Downregulation of ACE2 has recently been demonstrated to increase the severity of COVID-19. Therefore, WFA demonstrates real potential as a therapeutic agent to treat or prevent the spread of COVID-19 due to the reported interference in viral S-protein to host receptor binding and its lack of effect on ACE2 expression in the lungs.

Withania somnifera as a potential future drug molecule for COVID-19

“…It is considered an important herbal restorative in Ayurvedic medicine and is also known as 'Sattvic Kapha Rasayana', which can be used for various pharmacologic properties and could be a potential candidate for the management of COVID-19 as a safer alternative to currently available disease-modifying drugs such as hydroxychloroquine [4,8,9]. More than 40 withanolides, 12 alkaloids and rare sitoindosides have been discovered in W. somnifera [10][11][12][13]. A total of 69 (39 preclinical and 30 clinical) studies documented the safety and clinical efficacy of W. somnifera [9].…”

Role of Ashwagandha (Withania Somnifera) as Immunomodulator in Coronavirus in a pandemic – A systemic review

“…It suggests that the anti-in lammatory & antitumorigenic "properties may bind the viral spike (S) protein of SARS-CoV-2. WFA does not alter the expression of ACE2 in the lung of tumor bearing female mice" (Straughn and Kakar, 2020;Dhuley, 2001).…”

Medicinal Plants, Phytochemicals, and Herbs to Combat Viral Pathogens Including SARS-CoV-2

“…Apart from developing effective vaccines, therapeutics, and antiviral drugs, the potent antiviral applications of various plants, plant extracts and herbs are required to be endorsed and proliferated optimally by strengthening researches and development activities along with conducting appropriate clinical trials and validation experiments to combat COVID-19 pandemic and its high challenges posed [ 12 , 32 , 184 , 185 , 186 , 187 , 188 , 189 , 190 , 191 ]. Advances in the fields of biotechnology, immunology, biochemistry, pharmacology, pharmaceuticals, and nanotechnology may be warranted to their full potential for developing successful antiviral drugs and medicines out of these safe and valuable natural resources against SARS-CoV-2 [ 192 , 193 , 194 , 195 , 196 , 197 , 198 , 199 , 200 ]. Beneficial applications of medicinal values of plants and herbs could lessen the high incidences, devastating scenario, and public health concerns of SARS-CoV-2/COVID-19.…”