Treatments and Prophylactics for a Global Emergency Alert: COVID 19 using Allopathic and Indian Phytomedicine

Aravindhanathan Venkatesan1, Sudhakar Kothandan1, Arun Radhakrishnan1, Gowthamarajan Kuppuswamy*1, Dhanabal Palanisamy2, Balasubramanian Somanathan3, Suresh Bhojraj4 1Department of Pharmaceutics, JSS College Of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India 2Department of Pharmacognosy, JSS College Of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India 3Faculty of Life Science, JSS Academy of Higher Education & Research, Mysore, Karnataka, India 4JSS Academy of Higher Education & Research, Mysore, Karnataka, India


INTRODUCTION
COVID 19 (Corona Virus Disease , 2019) also called as severe acute respiratory syndrome novel corona virus which brings the health crises to global emergency alert in more than 200 Countries, areas or territories, which con irmed more than 12 lakhs positive cases around the world wide population with 69 thousand death (fatality:5-6 %). The China National Health commission has reported 17 deaths caused by nCoV on January 22, 2020 initially. WHO declared this situation as global emergency alert and suggest both developed and developing countries  WHO, 2020;Singhal, 2020;Middle East Respiratory Syndrome Coronavirus, 2020) to quarantine the people to eradicate the spreading of Novel Corona Virus (nCoV) through human to human interaction. (Corona Virus Disease , 2019) Various levels have been evolved in radiating the nCoV (Thacker, 2020 Centers for disease prevention and control explained person to person COVID 19 sprea were it is thought to spread through the infected person's respiratory droplet when he starts couging or sneezing, resembling the spread of in luenza. (Centers for Disease Prevntion and Control. Available, 2020) nCoV shows the symptoms (fever, cough & shortness of breathing) in the host within the time span of 14 day within which the chance of infection would be possible if a person touches an infected surface and then touches his or her eyes, nose, or mouth. Middle East Respiratory Syndrome Coronavirus (2020) The patients are categorized into symptomatic infection and asymptomatic infection but both the groups will be having the same viral load. (Siddhartha, 2020). Moreover, nCoV 19 was similar to that of their ancestors namely, SARS CoV (severe acute respiratory syndrome coronavirus) and MERS CoV (Middle East respiratory syndrome coronavirus) and their deaths and mortality rate as given in Tables 1, 2, 3, 4, 5 and 6.

COVID 19
WHO categorized COVID 19 as a β genus which belongs to the group 2B that was con irmed by the case report of 9 patients which exhibited 99.98 % similarity in sequence identity and 99.8-99.9 % nucleotide identity through which the new strains of nCoV has been revealed. New Strain is similar 76.5 % to SARS CoV and MERS 50 %. (Ren et al., 2020;Lu et al., 2020;Hui et al., 2020) it is generally believed that the incubation period for COVID 19 is 3 to 7 days (average) with shortest of 1 day and longest of 14 days. These viruses are the enveloped positive sense RNA virus and have the spike like projection (Crown) with the overall size of about 60 to 140 nm. Since it have the crown like projection under electron microscope, it called as the "Corona Virus". (Singhal, 2020) Basically there are four corona virus (HKU 1 , NL6 3 , 229 E and OC 43 ) which have been circulating in the human and causes mild respiratory syndromes.
All the ages are susceptible and can cause the differential clinical features from the asymptomatic state to ARDS (acute respiratory distress syndrome) followed by multi organ dysfunction. The most common clinical features are cough, sore throat and dificulty in breathing which also possess fever (not in all), fatigue and myalgia. This causes the pneumonia in 1 st week and causes respiratory failure and death by extreme progression of human immune system response through the cytokines including IL 2 , IL 7 , IL 10 , GCSF, IP 10 , MCP 1 , MIP 1A , and TNF α .  Death and adverse outcomes are most common in elder patient (50-70%  Daily once in empty stomach for three days.   Daily once in empty stomach for three days.

Signi icant receptor for SARS CoV binding and potential approaches to address COVID 19
Crown proteins of the SARS CoV-2 possess the similar receptor binding domain to the SARS CoV in the ACE II Receptor which was explained by the Xu et al.
(2020) through the computer modeling. More over the ACE II receptor are widely spread in the epithelial cells of the lungs, that makes the lungs to become most susceptible organ in the human body. Hence to treat or prevent COVID 19, the following potential approaches can be given to manage the same. (Xu et al., 2020) Approaches in the SARS Cov-2

Soluble form of ACE II
By administering the excessive soluble form of ACE II will interact with the CoV 2 and may aid the down regulation of ACE II and protect the lungs from the injury and may slow down the entry of virus Imai et al., 2005).

Crown vaccine/ Spike Vaccine
By complete understanding of the various sub units in the Spike/ crown parts in the virus may help to produce the appropriate vaccine and will pave the way for demolishing it (Zhang et al., 2020).

ACE II Inhibitors
An atomic level understanding of the SARS CoV 2 to the ACE II has been performed recently, they postulated ACE receptor blocker or other vaccins can be develoed to manage this global emergency.
Antihypertensive agents that regulate the blood pressure by inhibiting the ACE receptors are readily existing in the market. So these medicines are hypothesized to repurpose the restriction in viral entry and prevent the infection. But in other hand due to its up regulation of ACE II receptor that will produce more reception to nCoV, no cases has been reported to continue the treatment with this medicatio which was reported by European society of cardiology. (De and Simone, 2020)

Current Treatments for this Global Emergency
Besides identi ication of so many treatments and intervention, no medication has been approved, represents the reposition of other therapeutic agents to treat this emergency alert and to decrease the mortality caused by COVID 19.

Antiviral activity of Indian natural herbs
They are many natural herbs and their respective active substance that can be used to treat the viral disease. The following Indian Traditional medicinal herbs can be used to treat COVID 19.

Gymnemasylvestre
Gymnemic Acid is the potent antiviral compound with suf icient scienti ic studies has been reported since 1968 against in luenza (Sinsheimer et al., 1968). Recently, Vimalanathan et al studied the same compound against Human Corona virus, which showed greater activity against the SARS CoV with the concentration of 0.5 µg/ml (Vimalanathan et al., 2009). Hence using this herbal extracts will play a promising role in controlling COVID 19.

Achyranthesaspera
Leaves extract of the L. aspera revealed the anti-viral activity against the Epstein-Barr virus in in vitro studies (Radha and Vijayaraj&amp;vidhya, 2016) and their anticoronal activity was recently evaluated. Since the SARS CoV 1 & 2 are similar in their characteristics, the L. aspera can be used to treat the COVID 19. (Vimalanathan et al., 2009)

Other medicine plants
Clerodendruminerme, Pergulariadaemia,Sphaeranthusindicus, Crescentiaalata are the indiantrational plants with the recent studies reported positive against the activity Human Corona virus hence this medicinal plants can be used for the COVID 19 treatment (Vimalanathan et al., 2009).

AYUSH recommendations in the race of this Global emergency alert
(Government of India, AYUSH. , 2020) Press Information Bureau, Government of India, AYUSH has conducted meeting on 7 th March, 2020. In the various vision of AYUSH, few medications and approaches has been suggested from the individual holistic Indian traditional medicinal systems. The various medications, dietary management and prophylactic intervention were recommended for the treatment of COVID 19. Tulsijuice or infusion (Ocimum sanctum), Guduchi juice/decoction with honey (Tinosporacordifolia), Ginger juice/decoction with honey (Zingiberof icinale) and Turmeric powder in honey or warm milk (Curcuma longa) can be used as the prophylactics. Causative factors and their respective symptoms can be avoided by the boosting the immune system through the treatment of Ayurveda.
With the above mentioned recommendations, some of the general preventive measures has to be taken for the health crises. (Government of India, AYUSH. , 2020)

Observation of Best and better personal
Hygiene.
2. Practice frequent hand wash with soap which prevent the entry of SARS CoV 2 or any other disease causing agent by touching eyes, nose or mouth.
3. Wear face mask or cover the mouth when coughing or sneezing.
4. Avoid the close conduct with the people who are feeling sick, dif iculty in breathing.
5. Avoid the conduct with pets or any other animals.
6. Avoid travel to the farms or garden, animal slaughter house or markets.
7. Use the hand sanitizer with Alcohol.
Other hypothetical approaches to aid this race to manage COVID 19

Aerosol related formulation approaches
Since Lungs are the most vulnerable organ for SARS CoV 2, the administration of drug by the aerosol through oral route may produce the immediate therapeutic actions. Moreover the Nitric oxide gas inhalation for the patient suffered by SARS CoV 2 can be given, which showed the greater antiviral activity against the SARS CoV in 2003. Hence the same treatment was referred by the health professionals and the respective clinical trials were also in progress for the treatment of COVID 19. (US National Library of Medicine, 2020)

Approaches associated with natural herbs
Preferable remedies that can be used against COVID 19 are ACE inhibitors, TMRASS 2 inhibitors and CD 13 inhibitors of the Indian herbs can be selected and can be takenin the form of steam. Steam will produce immediate on set of action once it reaches the mucosal layer of the epithelial tissues in the lungs.
Mycleayecordata (plume poppy) is used in the Chinese traditional medicine, which inhibit the CD 13 receptors that pave the reception to the CoV. The pathogenesis of the CD 13 receptor associated SARS CoV 2 was not explored. But by inhibiting this receptors we can provide the prophylactic action for the COVID 19.
Curcumin polyphenols has been reported as the potent HIV 1 and HIV 2 protease inhibitor. Since it has proven antiviral activity in the many viruses, it can be utilized for the SARS CoV 2 treatment. (Verma, 2019) Nicotinamine (Vitamin B3) is effectively preventing the tissue damage in the Lungs (Shi et al., 2020) which can be given as the dietary supplement for the patient.
Glycyrrhizin an active constituent of liquorice root and considered to be a potent antiviral agent that was priorly used to treat the In luenza virus that can be used for treating COVID 19 too. (Wang et al., 2015) Recently using Molecular docking and Computer modelling, Chen and Du (2020) suggested some of the compounds which have shown greater af inity towards ACE II receptors by the vander waals force. baicalin, Scutellarin, Hesperetin, glycyrrhizin and Nicotianamine will play the promising role for the complete eradication of COVID 19. (Chen and Du, 2020)

CONCLUSIONS
Epidemic of the 2020 causes huge impact throughout the world. In developed countries particularly in US more than 3.3 lakhs cases were reported on 6 th April, 2020. In other hand, Wuhan in china was slowly recovered by quarantining their people and taking timely action by their respective governing bodies. This virus is not new for this world, the same strains SARS CoV was reported in 2003 followed by MERS CoV in 2012. But due to lack of prediction on the CoV, we paid more than 50 thousand deaths and it may increase the count in the upcoming days. Therefore, the more research on these types of viruses should happen in future to predict and focus the upcoming health crises. Thereby controlling the disease and repositioning of the Pharmaceuticals can be done in the shorter span of time.

ACKNOWLEDGEMENT
The authors would like to thank Department of Science and Technology-fund for improvement of science and technology infrastructure in Universities and Higher Educational Institutions (DST-FIST), New Delhi for their infrastructure support to our department.