COVID 19: Growth analysis, similarity study with HIV and its prevention through flavone rich natural foods

The Coronavirus borne disease COVID 19 has evoked a global crisis which ranges from human health to forecasted economic slowdown in recent times. Originating from China the pandemic has subsequently spread to several developed as well as developing countries including France, Australia, Spain, USA, Germany, Italy, India [1,2]. COVID 19 has taken the life of 62,784 persons while 1,133,758 many people are affected as far as global scenario is concerned as on 05.04.2020 based on the situation report published by World Health Organization (WHO).


Introduction
The Coronavirus borne disease COVID 19 has evoked a global crisis which ranges from human health to forecasted economic slowdown in recent times. Originating from China the pandemic has subsequently spread to several developed as well as developing countries including France, Australia, Spain, USA, Germany, Italy, India [1,2]. from animals to humans causing signifi cant mortality [2]. The reproductive capacity of 2019-nCoV is found to be more than the earlier SARS coronavirus [1,4]. But the real source of this pandemic, its pathology and pathogenesis, idea of curative vaccines are all seem to be in dark till now.
The transmission pattern of this pandemic outbreak involves direct contact, droplets and airborne routes. From Wuhan, China this disease has rapidly spread over distant nations like France, Australia, Spain, USA, Germany, Italy, India [2,5]. COVID has characteristic clinical symptoms including fever, chills, cough and respiratory troubles. The most prominent pathological fi ndings in this case are shortness of breath and alveolar damage [6]. Apart from the worst affected epithelial cells of respiratory track, mucosal cells of the intestines, tubular epithelial cells of the kidneys, neurons of the brain, and several types of immune cells also get affected during the course of illness [6].
Hence, it is urgent need of the hour to encounter the virus by preventing it from further spread. Since vaccine of the virus is yet to be discovered, it would be the safest way out to prevent the virus through different means from affecting the human body. Therefore, several protective measures have been suggested by the WHO, Governments, NGOs etc. in this regard. Apart from social distancing and self hygiene, exploration of effective antiviral agents that are easily consumable through dietary intake has become essential. Hence, through this paper we have analyzed severity of the growth profi le of COVID 19, studied its structure and similarity with HIV and suggested chemically viable dietary solution which can resist the viral reproduction within the host cell.

Growth analysis of COVID 19
In the present paper, the growth profi le of COVID 19 has been analyzed in two segments i.e. one is for India and another is for the World consisting of all affected countries [5,7,8]. For each of the segments, the analysis has been done in terms of two factors viz. i) total COVID 19 positive cases and ii) total COVID 19 death cases.
The data was collected from the situation reports published by World Health Organization (WHO) in its website (www.who. int) from 30.01.2020 i.e. the day on which fi rst confi rmed case of a COVID 19 positive was reported in India to 04.04.2020. The data pertaining to India and the World has been tabulated in Considering the fact that the actual corona threat to India is cumulative in nature which urges for disposing of all outstanding cases, the parameter for testing was taken as 'total confi rmed COVID 19 cases' and not the 'new COVID 19 cases' on a particular day. The test period was selected from 01.03.2020 to 04.04.2020 and analyzed in a week wise manner for cases in India and the World. The tests were done with 5% level of signifi cance. The P values obtained in the tests for paired two weeks mean COVID positive and death cases in India are presented in Table 2 (P values of t tests-Paired two weeks mean COVID cases in India).
Similarly, it was statistically analyzed whether COVID positive and death cases are signifi cantly increasing in the world for a test period of 01.03.2020 to 04.04.2020. The null hypothesis (H 0 ) and alternate hypothesis (H 1 ) were as under: H 0 : The COVID cases are not signifi cantly growing week by week in the World.   The P values obtained in the tests for paired two weeks mean COVID positive and death cases in the World are presented in Table 3 (P values of t tests-Paired two weeks mean COVID cases in the World).
Further, trend analysis was done for assessing the growth pattern of total positive cases in India. The graph (Figure 1) was plotted considering "Number of total COVID 19 positive cases" in the vertical axis and "Corresponding date" in the horizontal axis for analysis of spread of corona positive cases in India.
Similarly, the graph was plotted for cases in the World ( Figure   2) The charts (Figure 3 for India and Figure 4 for World) were plotted considering "Number of total COVID 19 positive cases Vs. death cases" in the vertical axis and "Corresponding date" in the horizontal axis.

Prevention through diet
Through literature survey and virtual screening from a set of available group of organic compounds, we have recommended one class of compounds as anti viral agent for 2019-nCoV and suggested its natural sources in fruits and vegetables.   Table 3: P values of t tests-Paired two weeks mean COVID cases in World.   with other viruses to understand its host specifi city. Four new types of insertions in the S protein of 2019-nCoV have been observed when compared to its nearest neighbour SARS-CoV [9][10][11]. These insertions have been preferably acquired by 2019-nCoV promoting its additional survival capacity and infectious nature. Till date sequence alignment studies of spike proteins fi nd several similarities between gp120 and Gag protein of HIV-I [2,9,11]. In HIV, gp120 is responsible for recognizing the host cell and Gag protein performs host membrane binding and packaging [11]. Therefore the novel corona virus of 2019 can be said as the mutated version of previously reported coronavirus showing host specifi city towards human. 3D modeling of protein structure displayed that these unique insertions of 2019-nCoV are present at receptor binding sites and thereby they increased the range of host cells to be infected by these novel viruses [11].

Paired t tests for mean COVID cases in the
Plant products like fruits and vegetables are the good source of various metabolites that have therapeutic values as antiviral agents. They can arrest viral proliferation within the host cell either by inhibiting receptor binding and membrane fusion or by modulating intracellular replication, transcription and translation processes of viral genome. The primary purpose of this article is to search for effi cient inhibitor of 2019-nCoV that are easily consumable as fruits and vegetables in our day to day life and having no side effects as such. Therefore, we have recommended a group of fl avonols and fl avonol rich foods to combat COVID-19.
In taxonomical terms it can be said that corona virus belongs to the family coronaviridae and is a class IV virus. Its genetic material, single stranded RNA can act as m-RNA and thereby can replicate itself and synthesize proteins. Therefore, an effective drug target to hinder proliferation of viral genome can be the main protease, 3-chymotrypsin-like protease [3CLpro] and papain-like protease [PLpro] due to their major role in processing the polyproteins, translated from viral RNA. Reports are there identifying polyphenols from Broussonetia papyrifera as coronavirus protease inhibitors [12]. Researchers have shown that among ten isolated compounds papyrifl avonol was the most potent inhibitor of PLpro with an IC50 value of 3.7 lM [12]. Cheng-Wen Lin, et al. also reported anti-SARS-CoV 3CLpro effect of Isatis indigotica root-derived compounds and several herb-derived phenolics like aloeemodin, quercetin, hesperetin and naringenin using both cell-free and cellbased cleavage assay [13]. Linlin Zhang, et al. reported X-ray crystallographic structural analysis of native anti-SARS-CoV 3CLpro protease and recommended an -ketoamide inhibitor as effective protease inhibitor [14,15]. In case of co-crystal ligand, the key interacting residues were identifi ed to be Gly143, Cy145, His 164, Glu166, Gln 189 and Thr 190. By virtual screening from a set of available group of organic compounds, we have identifi ed fl avone based compounds as a potential lead anti-viral agents due to its ability of interactions with receptor by H-bonding and Pi-stacking interactions.  compounds act as good anti-oxidant and free radical scavenger due to their number and position of hydroxyl groups. From chemical intuition it can be said that among the three mentioned fl avonols, Luteolin is the most potent due to its most activated carbonyl functional group. Hence, Luteolin and associated Flavones can be thought of preventive measure of COVID 19. These compounds are mainly found in herbs and sometimes suggested as dietary supplements. Luteolin is not so toxic and it has the ability to cross blood brain barrier and capacity to suppress neuroinfl ammation. include more fl avone rich fruits and vegetables in our regular diet which will help in boosting up our immunity against 2019-nCoV. Since the vaccine of COVID 19 is yet to be discovered, prevention is the best tool we have to fi ght the pandemic and downturn the dangerous growth trend of COVID 19.