Introduction
Three different strains of CoV (Coronavirus) have crossed the species obstruction to cause fatal pneumonia in humans since the start of the 21st century: SARS-CoV (severe acute respiratory syndrome) (Drosten et al., 2003), MERS-CoV (Middle-East respiratory syndrome) (Zaki et al., 2012) and SARS-CoV-2 (causative agent of COVID-19) (Huang et al., 2020), first emerged in the Wuhan city, December 2019, in the province of Hubei, China, was isolated and sequenced in January 2020. An ongoing eruption of COVID-19 (atypical pneumonia) has affected more than 36, 471, 856 individuals and claimed 1,061,788 lives in 213 countries as of October 8, 2020. It became a super- hot spreading virus, such that the World health organization declared it as a Public Health emergency of International concern on January 30, 2020 (Zhou et al., 2020). MERS-CoV virus was reported to be originated from bats, where camels acted as a reservoir host (Haagmans et al., 2014). SARS-CoV and SARS-CoV-2 are genetically closely related and believed to be originated from bats, whose intermediate reservoir host is unknown. The persistent spillovers of CoVs in humans besides the recognition of numerous coronavirus strains in bats, including SARS-CoVs, imply the future continues zoonotic transmission events (Anthony et al., 2017; Ge et al., 2013; Zhou et al., 2020). In addition to an extremely pathogenic strains of CoV; MERS-CoV, SARS-CoV and SARS-CoV-2, belonging to same genus (b-coronavirus), four other low-pathogenic endemic strains in humans are also reported: HCoV-229E, HCoVHKU1, HCoV-NL63 and HCoV-OC43.Till date, no vaccines or therapeutics are available against any human infecting strain of CoVs.
CoV enters into the host cell via transmembrane spike (S) made up of glycoproteins which helps in forming homotrimers protruding from its surfaces (Tortorici & Veesler, 2019). S is comprised of two functional subunits (S1 and S2) which permit its efficient binding to the host cell surface receptor and also, helps in viral and cellular membranes fusion (Burkard et al., 2014; Kirchdoerfer et al., 2018; Millet & Whittaker, 2014). ACE2 (Angiotensin converting enzyme 2) has been reported to be a central component mediating the viral entry into the host cell. ACE2 is expressed in gastrointestinal tract, endocrine tissues, kidneys, liver/gall bladder, testis and to smaller extents in lungs. The Receptor Binding Domain of spike proteins induces conformational changes in ACE2 receptors, which further dissociates the S1 subunit of the spike and hence initiates host cell membrane fusion. Therefore, ACE2 might play a vital role in drug designing. Amidst all these few names came into the picture mainly hydroxychloroquine, arbidol, remdesivir, and favipiravir etc. these drugs are taken as potential candidates according to National Health Commission (NHC) of the People’s Republic of China. But none proved to be successful in severe respiratory distress or each one works differently according to an individual’s immune system.
Traditional and herbal medicines are the part of Indian medicines since ages. The full potential and capabilities of Indian system of medicine is still unmapped. Exploring herbs and medicinal plants are one of the hopeful platforms to combat the disease and decrease the acute side effects of chemical agents (Khare, 2004). One such Indian plant which comes under the category of spices is Nigella sativa. It belongs to the family Ranunculaceae. The herb is available in the Indian households by the name of Black caraway or Kalonji. It is considered as curative herb and in Islam it is one of the miracle plants which is described as universal healer (Goreja, 2003). N. sativa has proven antiviral, antihypertensive, liver tonics, diuretics, digestive, anti-Diarrhoeal, appetite stimulant, analgesics, anti-bacterial properties (Abdel-Sater, 2009; Abdel-Zaher et al., 2011; Abel-Salam, 2012; Assayed, 2010; Boskabady et al., 2010; Salem, 2005). The more attributed role of Black caraway includes antidiabetic, anticancer, immunomodulator, analgesic, antimicrobial, anti-inflammatory, spasmolytic, bronchodilator, hepato-protective, renal protective, gastro-protective and antioxidant nature. The main constituents include thymoquinone, thymol, carvacrol, γ-terpinene and p-cymene etc. (Sahak et al., 2016; Ahmad et al., 2013).
In the current study, we have deciphered the mechanism of action of N. sativa for its usefulness against SARS-CoV-2. Since ACE2 is a target site for SARS-CoV-2 therefore a network was generated around this protein to depict a disease network and N. sativa constituents was used as a treatment network. This study uncovers the targets of phytochemicals and their mode of action and responsible protein targets for their efficacy. The study revolves around the pathways and processes which needs to be targeted in COVID-19. N. sativa is a new hope and can be used as therapeutics for combating the disease.