Coronaviruses are well known pathogenic organisms of humans and animals which cause a broad spectrum of respiratory, gastrointestinal, neurological and systemic diseases¹.

Deriving its name from the word ‘corona’² meaning outer fringe(because of the presence of spiky outer enveloped protein coat), coronaviruses belong to the family Coronaviridae which are further subdivided into four genera namely, Alphacoronavirus, Betacoronavirus, Gammacoronavirus and Deltacoronavirus³.

Table (1):
Recognised strains of Coronavirus affecting humans.

Evolution of Covid-19
The genera Alphacoronaviruses and Betacoronaviruses contain viruses infecting both humans and animals (Table 1)^4,5 while the genus Gammacoronavirus and Deltacoronavirus contains viruses specifically infecting animals (Table 2)⁴; the first one being seen in whales and birds, and the latter ones are isolated from pigs and birds⁴.

Table (2):
Recognised strains of Coronavirus affecting animals.

Discovered in early 1930’s as a pathogen causing mild respiratory infection in domesticated chickens¹ coronaviruses gained major attention in 2003 after the emergence of SARS(Severe Acute Respiratory Virus) which caused a major global epidemic wiping out thousands of global population.

Before 2003 epidemic was inked in the history of humankind, coronaviruses were known to cause mild respiratory infections. It was the first time, when coronaviruses were seen posing such a serious threat. This was a game-changing event which led to various researches. As reported, SARS was known to be caused by cross species transmission- from bats to humans.

Since then, coronaviruses are seemingly undergoing variety of mutations and leaping into humans causing infections, both mild and severe. After SARS, four more strains of coronaviruses have been recognised till now of which two strains namely, HCoV HKU-1 and NL63 are known to cause mild respiratory disease while two strains namely, MERS-CoV and SARS-CoV-2 have caused epidemics affecting human population in large numbers and severity¹. All the seven strains of coronaviruses recognised in humans are known to jump to humans from animals crossing species barrier (Fig. 1). The progenitor viruses of the recognised strains are seen in different host animals. HCoV- NL63, HCoV-229E, MERS- CoV and SARS- CoV are considered to have their origin in bats while HCoV-HKU1 and HCoV-OC43 are most likely to be originated from rodents^3,6,7. Domesticated animals may play important roles as intermediate hosts which enable transmission of these viruses from their natural hosts to humans. SARS-CoV finds its intermediate hosts in civets^3,8,9, HCoV-229E in camelids while MERS-CoV most likely found its way to humans through dromedary camels^3,10.

The latest recently recognised strain of all, SARS-CoV-2, was recognised in December 2019, in Wuhan city of China. Seeing its genomic similarity with SARS-CoV, it is thought to have paved its way to humans from animals through the live animal markets of China. The two probable theories of the origin of the virus gives bats^11-13 or pangolins^{13, 4} as the natural host of the virus, bats being the most closest. The virus, likely, then mutated and evolved to spread most probably though an intermediate animal bridge to humans and now human to human transmission can be easily noted.

Being of the common origin as of SARS-CoV, it was hypothesized that the virulence of SARS-CoV-2 will also be affected by the increasing temperatures especially above 39°C (same as in case of SARS-CoV). According to the various studies conducted in this regard, the result remains inconclusive. According to a study conducted in China, COVID-19 mortality decreased with increase in ambient temperature (above 39°C) along with increased absolute humidity¹⁵. A study conducted by Wang et al.¹⁶ showed reduction in transmission of the disease while studies conducted by Ye Tao et al.¹⁷ and Zhu et al.¹⁸ showed ambient temperature had no effect on the transmission of SARS-CoV-2.

Complementary Medicine
Since the emergence of human race, plants have been the source of countless compounds having medicinal properties and lead to drug discovery. Since the ancient times, Indian Ayurveda, Traditional Chinese Medicine Literature, ancient Egyptian Ebers Papyrus all gives description of various plants and herbs having medicinal properties which are even today used all over the world for various health benefits. Different plant compounds act as immune boosters and can act as antibacterials, antivirals as well as antifungals. The coronaviruses encodes various proteins which enables its functioning. Many plants produce compounds interfere with these proteins and can become a target for drug development. Since the gene sequence of COVID-19 has very high similarities between the man proteins of COVID-19 and in SARS or MERS, thus previously reported anti-SARS or anti-MERS natural compounds may become a valuable guide to find the affective anti-COVID-19 herbal plants (Table 3).

Table (3):
Plant products effective against various strains of Human Coronavirus.

There are more than a dozen of proteins which are encoded by coronavirus. Some of these proteins are essential to viral entry and replication. Papain-like protease (PLpro), 3C-like protease (3CLpro) and spike protein are the well studied proteins so far. All of these three proteins make attractive targets for drug development. Some of the herbal plants have been screened in silico by Narges & Neda 2020 to find the inhibitors for COVID-19 proteases, which could be an effective strategy for combating against this deadly virus. Due to the strong interaction of these natural compounds with enzymatically conserved regions and specific functionality, these compounds can be considered as effective antiviral drugs due to their natural origin and less likely to produce adverse effects if they enhance the interaction. Out of the eight tested secondary compounds curcumin was found to have strong interaction with protease of COVID- 19¹⁹. In another studies in silico screening with AI has been performed. It is a very fast method of screening reducing the cost of experiment as well as few human trials are required which leads to a fast development of drug²⁰.

Until now, many existing allopathic drugs are also being tried continuously which may prevent worsening of the clinical condition of the patient and provide them early relief. Some of them being given to the patients include remdesivir, lopinavir, chloroquine or hydroxychloroquine and interferon beta-1a. Recently, convalescent plasma therapy is being tried²¹. But all these medicines have many potentially serious side effects thus limiting their use to critical patients only. Moreover, the efficacy of these medicines has not yet been proven and thus are restricted to compassionate use only²² (Table 4).

Table (4):
Commonly used Allopathic Medicines in COVID-19.

Randomised Control Trials are continuously being done to see and prove the efficacy of these drugs and to find an appropriate effective treatment. One of the biggest international clinical trials is being conducted by WHO which has been given the name “Solidarity”. Seeing the urgency of the need of an effective treatment against the COVID-19, this trial is said to reduce the normal time taken by 80%. Four regimens are currently included namely, remdesivir, lopinavir with ritonavir, chloroquine or hydroxychloroquine and lopinavir with ritonavir with interferon beta-1a²³.

Although same is the case with complementary medicine and their use is dependent upon their recorded effects in the treatment of SARS and MERS and upon the various small clinical trials and that their efficacy against COVID-19 is not yet proven, but the lack of potentially serious side effects gives us a possible and much needed window for their use in the treatment of COVID-19 not only in critical patients but also in patients with mild clinical disease. Although complementary medicine cannot replace modern medicine but can act as its supplementary. The integrated treatment can be clinically more effective and decrease the suffering of the patient in both time and severity. National Health Commission of the People’s Republic of China, on Feb 17, reported that 60,107 confirmed COVID-19 patients were successfully treated with integration of Western medicine and Traditional Chinese Medicine^24,25. Also, traditional pool can be exploited as a prophylactic medicinal source against the disease especially in high risk population by boosting up immunity, blocking the infection, cutting off the inflammatory storm and promoting repair of the body²⁴.