The Coronavirus disease outbreak during December 2019 in the Wuhan city of China was caused by SARS-CoV-2 and has been declared as COVID-19.[1, 2] COVID-19 was thought to have emerged from a seafood market from an unknown species, causing the virus's emergence and symptoms to be comparable to pneumonia. The confirmation of the human-to-human transmission of the contagious virus was made by the National Health Commission of China in late January. As SARS-CoV-2 began to spread across international borders, affecting the population of multiple countries, WHO designated it an Internationally concerned Public Health Emergency and declared as a global pandemic in March 2020.[3, 4]
Based upon the sequence resemblance of the SARS-CoV-2 nucleotide, it is considered as a Beta coronavirus having high similarity with the well-known and aggressive strains of human coronaviruses (HCOVs). The nuclear material of SARS-CoV-2 was found to be a long positive-sense single-stranded RNA encoding two discrete types of structural as well as non-structural viral proteins.[1, 2] The 5′-untranslated region (5’UTR) and a replicase complex encode for viral structural proteins like spike, nucleocapsid, matrix, and envelope, while 3′UTR and several unidentified open reading frames encode for viral non-structural proteins like protease, phosphatase, and polymerases.[1, 2]
COVID-19 is having initial symptoms of like cough, malaise, fatigue, fever, body aches, loss of smell or taste sensation, inadequacy, and shortness of breath followed by respiratory distress. The persistent viral infection affects not just the lungs, but also other key organs in the body, eventually leading to organ failure.[6–8] Coronavirus transmits from person to person through coughing and sneezing, which spreads to the nasal mucosa via airborne droplets, where it replicates narrowly in ciliated epithelial cells, causing cell damage and inflammation. The transmission of this virus was also observed from infected surfaces to individual’s hands, and then to their bodies.
Globally, more than 216 countries have been affected by the pandemic outbreak of COVID-19 till December 31, 2021. More than 287,022,026 confirmed cases of coronavirus affected people were reported with more than 5,447,886 deaths. According to WHO, China is the first country to report 1,02,083 confirmed cases of COVID-19 with 4636 mortalities. The thoroughgoing number of COVID-19 infections till date has been observed in the US with more than 55 million confirmed cases and 845,745 deaths, followed by India with more than 34 million confirmed cases and Brazil with more than 22 million confirmed cases. Even after eighteen months of the outbreak of the novel SARS-CoV-2 coronavirus, there is still no approved therapy or vaccine available for the cure of this lethal infectious disease. In light of the foregoing, it is critical to design a novel remedy to combat the worldwide epidemic crisis.
The viral main protease enzyme was identified to partake a significant function in the pathogenic entry within the host via ACE2 and may be exploited as a therapeutic antiviral drug target. Inhibition of viral main protease results in the restricting the entry of the pathogen to the host cell terminating the viral infection.[4, 5, 11] As a result, an inhibitor of the main protease is likely to be a successful treatment for COVID-19 pandemics over the world. The proven methodology for in silico screening of herbal leads to identify modest inhibitors of the viral main protease enzyme is depicted graphically in Figure 1.
Herbal medicine is a holistic medicine, being used for the management of several health problems for thousands of years. Herbal medicine inspired several drugs, such as artemisinine, paclitaxel, reserpine, morphine, quinine, emetine, aspirin, and many more, have been discovered for the treatment of numerous diseases. Most of the world population relies on herbal medicine as an alternative and complementary medicine for the management of diseases like COVID-19. In this context, several herbal medicines and their bioactive leads including Camellia sinensis (epigallocatechin gallate), Andrographis paniculata (andrographolide), Artemisia annua (artemisinin), Betula sp. (betulinic acid), Citrus sp. (hesperidin), Curcuma longa (curcumin), Ficus benjamina (biorobin), Glycyrrhiza glabra (glycyrrhizin), Mollugo cerviana (vitexin), Myristica fragrans (myricitrin), Piper nigrum (piperine), Radix sophorae (matrine), Stephania tetrandra (tetrandrine), Tinospora cordifolia (berberine), Torreya nucifera (luteolin) etc. have been explored through computational approaches for the treatment of COVID-19.[12–32] Hence, it inspires us to find such herbal leads through an in-silico computational approach for the management of the current pandemic situation. Thus, in the current investigation, putative antagonists of main protease enzyme of the SARS-CoV-2 were acknowledged using docking based computational screening of herbal-based ligands followed by their validation with respect to time by using molecular dynamics simulation in order to develop novel therapy to combat COVID-19.