Naturally Occurring Bioactives as Antivirals: Emphasis on Coronavirus Infection

Abstract

The current coronavirus disease (COVID-19) outbreak is a significant threat to human health and the worldwide economy. Coronaviruses cause a variety of diseases, such as pneumonia-like upper respiratory tract illnesses, gastroenteritis, encephalitis, multiple organ failure involving lungs and kidneys which might cause death. Since the pandemic started there have been more than 107 million COVID-19 infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and ∼2.4 million deaths globally. SARS-CoV-2 is easily transmitted from person-to-person and has spread quickly across all continents. With the continued increase in morbidity and mortality caused by COVID-19, and the damage to the global economy, there is an urgent need for effective prevention and treatment strategies. The advent of safe and effective vaccines has been a significant step forward in the battle against COVID-19, however treatment of the symptoms associated with the disease still requires new anti-viral and anti-inflammatory drug therapies. To this end, scientists have been investigating available natural products that may be effective against SARS-CoV-2, with some products showing promise in fighting several viral infections. Since many natural products are dietary components or are prepared as dietary supplements people tend to consider them safer than synthetic drugs. For example, Traditional Chinese Medicines have been effectively utilized to treat SARS-CoV-2 infected patients with promising results. In this review, we summarize the current knowledge of COVID-19 therapies and the therapeutic potential of medicinal plant extracts and natural compounds for the treatment of several viral infections, with special emphasis on SARS-CoV-2 infection. Realistic strategies that can be employed for the effective use of bioactive compounds for anti-SARS-CoV-2 research are also provided.

Keywords: COVID-19; Coronavirus; SARS-CoV-2; bioactive compounds; natural compounds.

FIGURE 1

Schematic representation of a Coronavirus replication cycle, SARS-CoV virus structure, and the molecular targets for naturally occurring plant extracts and their active compounds against on viral infection. For attachment with host cells, SARS-CoV S protein use the cellular attachment factor Angiotensin-converting enzyme 2 (ACE2) and the cellular protease Transmembrane protease serine 2 (TMPRSS2) for their activation. SARS-CoV enters into host cells via endocytosis and release its RNA genome inside the cell. Further early and late protein synthesis occurs. Finally, viral assembly and then release outside the cells via exocytosis. The natural compounds that can target at different stages of viral replication may inhibit SARS-CoV infection. Inhibitors derived from plant sources such as alkaloids, glycosides, phenolic phytochemicals, essential oils, coumarins, cinnamic amides, and oleanane triterpenes may provide great treatment. Schematic diagram of SARS-CoV virus structure represents the single stranded positive-sense viral RNA, Spike (S), Nucleocapsid (N), Membrane (M), and Envelope (E) protein. Bioactive compounds that can inhibit structural and non-structural proteins of coronaviruses can be used with inhibitors of viral replication cycle.

FIGURE 2

Schematic diagram of SARS-CoV-2 virus genome organization and viral proteases inhibition by natural compounds. The complete genome sequence is ∼30 kb long. Two viral proteases (PLPro and 3CLPro) are responsible for cleaving polyproteins into the functional individual Nsps such as helicase, RDRP and methylases. Nsp3 also known as PLPro is a papain like protease that cleaves Nsp1/Nsp2, Nsp2/Nsp3 and Nsp3/Nsp4 boundaries whereas Nsp5 also known as Mpro or 3CLPro is a serine like protease catalyzing the rest 11 cleavage reactions. Table 3 shows the natural compounds that are known to inhibit these viral proteases.