Highlights:
- The viral SARS-CoV-2 E protein can be a potential drug target.
- Screening the potency of Indian medicinal compounds as an effective inhibitor/drug.
- β-boswellic acid and Glycyrrhizic acid potential hit bioactives for anti-COVID-19.
- Herbal compounds found to be more efficient as anti-viral therapeutics
Emergence of sudden predawn of highly infectious deadly disease casted a shadow all around the world. Officially known as SARS-CoV-2, it is the third strain of coronavirus found to be inflicting humans tremendously with COVID-19 after Severe Acute Respiratory Syndrome (SARS) and Middle East respiratory syndrome (MERS) (Yang et al. 2020).
Pandemic outburst which began from China’s Wuhan, drifted its way to all over the globe. The fear of 2019 novel Coronavirus (2019-nCoV) kept soaring, gushing its path of infection to more than 200 countries. The journey of the virus started on 17th November from the city of Wuhan in Hubei province (Davidson 2020). With Thailand emerging as second nation confirming COVID cases, South Korea and Japan also were in the deadly trap by January 20. The next day, the USA with Washington State falling to its prey (Wood et al. 2020). January 24 marked the entry of European nations starting from France, capturing Italy by February 1.
The deadly scare of SARS-CoV-2 virus kept rising, though not taken seriously initially by World Health Organization (WHO), dismissing it as too early to call an emergency, however, later declared a global public health emergency by WHO chair on January 23, 2020. COVID-19 took huge toll on human lives all around the world within no time was announced as a pandemic on March 13, 2020 (Wu and Chiwaya 2020).
The COVID-19 took 111 652 lives amongst the 1 773 084 confirmed cases as on 13 April 2020 according to data compiled by WHO (2020a).
Structure of Coronavirus
The novel coronavirus is of animal origin mutated and then inflicted humans with devastating outcome (Westerbeck and Machamer 2020). The mode of transmission is through droplets of saliva or discharge from the nose of the infected person via coughs or sneezes to get through and attack the respiratory system (WHO 2020b; Cascella et al. 2020). The structure of coronavirus revealed that it carries three to four proteins in their envelopes (Fig.1 created with BioRender.com). The most abundant is type III glycoprotein M, composed of a short amino-terminal ectodomain, three transmembrane domains, and a long carboxy-terminal tail on the inside of the virion (De Haan et al. 2000). The E protein is a minor but essential component of virus. The CoV envelope E protein is an integral and small membrane that form ion channels-viroporin. It is pentameric in nature consisting of A, B, C, D, and E chains. The C-terminal domain is mostly α-helical. It features a single hydrophobic domain (HD), which is targeted to Golgi membranes for virion release and secretory pathway cascade (Schoeman and Fielding 2019).
The trimeric spike (S) protein forms the characteristic viral peplomers which are responsible for cell entry via virus-cell attachment and fusion. A subset of coronaviruses comprises a hemagglutinin-esterase (HE) protein, which exists as a disulfide-linked homodimer (De Haan et al. 2000; Schoeman and Fielding 2019; Collins 2020).
Mechanism of transmission of Coronavirus
The coronavirus replication cycle is depicted in Fig. 2 (created with BioRender.com). The replication cycle begins with virus entering the host cell via membrane fusion endocytosis. Release of viral genome occurs for multiplying and make copies. Viral structural proteins gets translated to lead way for maturation of virions pathway at the endoplasmic reticulum-Golgi intermediate compartment (ERGIC). The secretory pathway is regulated by the pH gradient, the cargo efflux is mediated by exocytosis. The main driving force, which gives the dramatic effects on this secretory pathway is regulated by CoV E proteins-cationic activity of viroporins (Westerbeck and Machamer 2020; Schoeman and Fielding 2019).
The significance of coronavirus envelope proteins is that it carries the structure of a conserved Golgi complex-targeting signal in it, it is a conserved region. It is essential for critical virus life cycle aspects- from production to maturation (Schoeman and Fielding 2019). The process of assembly, budding, envelope formation, and pathogenesis are being regulated by E proteins (Westerbeck and Machamer 2020). The E protein is region where interactions with other CoV proteins and host cell proteins occurs. Hence, it stands as a very crucial link in COVID-19 transmission.
To contain spread of highly contagious COVID-19, the researchers are looking for a solution to treat the COVID infection. Unfortunately, till date, no medications or vaccines exist to cure COVID-19. Even a small promise of the therapeutic agent will be a boon, which is being sought after by scientists. Reports of usage of antiviral drugs, hypertensive medicines or even anti-inflammatory drugs or ACE inhibitors along with angiotensin-receptor blockers (ARBs) on account of preconceived notion and experience gained from SARS and MERS are still not recommended by any recognised regulatory body anywhere in the world that include the WHO or Centers for Disease Control and Prevention (CDC) (Collins 2020; Stebbing et al. 2020; Day 2020).
Without any clinical trials in humans, the approval of these medications without any testing is not advisable by clinicians, as they could lead to unintended and detrimental consequences. Hence, it would be too early to support or refute these claims.
The need of the hour is to dig into the basic fundamental aspects of virus structure, mechanism underlying its devastating spread, which would be vital in guiding, designing and developing effective drugs that can stop the pandemic which has become a global health crisis.
Based on studies on SARS, MERS and Ebola outbreaks, scientists are predicting that the conventional anti-viral drugs could be of benefit in curing the COVID-19 as well.
There are a few principal inhibitors which are also considered as promise for disease control for angiotensin converting enzyme 2 (ACE2), a human cell surface proteins which is the place of entry of virus via spike protein binding to that receptors (Collins 2020).
The urgency is to come up with an alternative solution to knockdown the level of COVID-19 grip. The present study deals with screening of the promising antiviral drugs from traditional Indian herbal compounds which can become the next drug to cure the COVID-19. The molecular docking insights would give a deep insight that will provide a basis for the design and development of therapeutics that specifically target this critical interaction of ligand (drug)-target (COVID proteins). Hence, this study proves to give a promising approach for prevention of COVID, and design of vaccines targeting the critical envelope (E) protein of coronavirus.
Understanding the role of the CoV E protein in virus is thus a paramount prerequisite for potential vaccines as well as in identifying novel antiviral therapeutics.