INTRODUCTION:

The coronavirus pandemic caused by novel SARS-COV-2 (Severe acute respiratory syndrome coronavirus 2) began in WUHAN city, CHINA In December 2019 and has spread worldwide.The first case in india was reported on 30^th January 2020 in kerala. A student from Thrissur district of Kerala studying in Wuhan University tested positive for the virus.As of today there are 34.8 million cases worldwide with total 1.03 Million deaths and 6.55 millions positive cases in India including total 102 K deaths in india.Presently in India the spread has outbreaked to a number approx 80,000 cases getting positive in a single day. We have gone into stage 3 that is community spread which is taking place in several cities of India.

Symptoms

Cold, cough, fever, loss of smell sensation and loss of taste, difficulty in breathing etc.

Viral Activity and Drug in Covid-19:

SARS-COV2 is a single starded RNA enveloped virus, target cells through the viral structural spike (S) protein that binds to the angiotensin-coverting enzyme 2(ACE2) receptor.The virus uses host cells receptors and endosomes to enter cells.A host type 2 transmembrane serine protease. TMPRSS2,facilities cell enteryviathe S protein¹.Once inside the cell, viral polyprotiens are synthesized that encode for the replicase transciptase complex.The virusthen synthesis RNA via its RNA dependent RNA polymerase structural proteins are syntheized leadindtocompletion of assembly and release of viral particles^2-4. These viral lifecycle steps provide potential targets for drug therapy.Promising drug targets include non-structural protien (eg, 3-chymotrypsin-like protease,papain- like protease, RNA-dependent RNA polymerase) which share homology with other cronaviruses (nCoVs). Additionally drug targets include viral entryandimmmune regulation pathways^5,6.

Remedisvir:

Remedisvir formally known as GS-5734 is a broad specturum antiviral drug, It is monophosphate prodrug that under goes metabolism to an active C-adenosine nuecleoside triphosphate analogue.It was noted that after adding Remdesivir, the polymerase enzyme stops adding more RNA subunits, stopping genome replication.These mechanisms are linked to Remdesivir’s ability to metabolize into an active form known as GS-441524 which is an adenosine nucleotide analog.The GS-441524 interferes with the action of viral RNA-dependent RNA polymerase and evades proofreading by viral exoribonuclease (ExoN). This decreases viral RNA production.Studies are still ongoing to understand whether the prodrug terminates RNA chains or it causes mutations in the RNA.Using Ebola virus studies, it was noted that the prodrug, Remdesivir, inhibited the action of RNA-dependent RNA polymerase, causing the elongation of the synthesized chain.

Azithromycin:

It has been shown that AZM has significant antiviral properties. In contrast with CQ or HCQ, its antiviral activity has been shown in vitro and/or in vivo on a large panel of viruses: Ebola, Zika, respiratory syncytial virus, influenzae H1N1 virus, enterovirus, and rhinovirus. Its activity against respiratory syncytial virus has been demonstrated in a randomized study in infants⁷. Azithromycin exhibited a synergistic antiviral effect against SARS-CoV-2 when combined with HCQ both in vitro⁸ and in a clinical setting. The mechanisms of the antiviral effect of AZM support a large-spectrum antiviral activity. Azithromycin appears to decrease the virus entry into cells. In addition, it can enhance the immune response against viruses by several actions. Azithromycin up-regulates the production of type I and III interferons (especially interferon-β and interferon-λ), and genes involved in virus recognition such as MDA5 and RIG-I. These mechanisms are universally involved in the innate response against infectious agents, and potentially against SARS-CoV-2.

The immunomodulation properties of AZM are the rationale of its use against inflammatory manifestations leading to interstitial lung disease^9,10. SARS-CoV-2 has been shown to exacerbate the inflammatory response of its host, leading to serious damage of lung interstitial tissue¹¹. Patients with severe COVID-19-associated pneumonia may exhibit a syndrome of systemic hyper-inflammation designated as a cytokine storm¹².Cytokine profiles of patients with severe COVID-19 have been compared to those of patients with moderate forms and have shown a notable increase in some pro-inflammatory cytokines such as interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, IL-17, and tumor necrosis factor-α^11-13. Therapeutic approaches targeting only IL-6 have been proposed but may be double-edged because the timing of its administration might adversely affect viral clearance¹³. By contrast, AZM shows an interesting immunomodulatory profile by inhibiting several cytokines involved in COVID-19 severe respiratory syndrome. Indeed, AZM regulates and/or decreases the production of IL-1β, IL-6, IL-8, IL-10, IL-12, and IFN-α^14,15. Hydroxychloroquine also has immunomodulatory effects, and has been reported to decrease IL-1, IL-2, IL-6, IL-17, IL-22, IFN-α, and tumor necrosis factor^16,17. Azithromycin and HCQ both decrease the production of major inflammatory cytokines such as IL-1 and IL-6. However, the different profiles of immunomodulation between the two drugs may be crucial for selecting one of them for the treatment of COVID-19, in relation to the pathogenicity of the virus. Indeed, HCQ may decrease IL-2 levels but not AZM, while AZM may decrease IL-8 levels but not HCQ.

Adjuctive therapies:

1. Plasma therapy

Convalescent plasma therapy uses blood from people who've recovered from an illness to help others recover. Blood donated by people who've recovered from COVID-19 has antibodies to the virus that causes it. The donated blood is processed to remove blood cells, leaving behind liquid (plasma) and antibodies. These can be given to people with COVID-19 to boost their ability to fight the virus.

2. Steam and gargles

Steam inhalation is traditionally used as a home remedy for common colds and upper respiratory tract infections. The steam loosens mucus, opens nasal passages, and reduces mucosal inflammation, or the heat inhibits replication of viruses.It acts in a number of ways to relief the congestion caused in COVID19.

3. Paracetamol

To lower the body temperature.

7-Pointer Healthy Lifestyle:

1. Hygenic way of living-

Reguraly washing and sanitising hands and your house or workapsce, also wearing mouthmask, gloves and headcapes while going out for work or market,also try to take bath after coming from outside or market like crrowded places. Wearing personal protective equipment kit if visiting doctors,for health proffesionals specially while treating patients,while travelling or coming in association with COVID patients. Best rule is to consider everyone universally as positive to keep yourself negative, so that you take all precautions.

2. Balanced and healthy diet-

On time meals,with proper and needed nutrional food to boost up your immunity.Avoid junk food and outside prepared food.Increase the intake of salads,fruits,dal, green leafy vegetables, milk with haldi, dry fruits, grains.A balanced diet which constiutes of all vitamins, minerals,fat, fibre and protiens along with all needed essential amino acids.

3. Proper and Deep Sleep-

Toallow your body immunity to heal your body you need to allow it to rest for 6-8 hour, out of which body goes in deep sleep for 2hours only. In the sleeping state the body energies affectively work in healing all body damaged and defective cells.So sleeping for 6-8 hours a day and everyday on time, early to bed and early rise is must.

4. Excercise and yoga-

Regular excercise and yoga keeps your body active and healthy, it releases all toxins from body in form of sweat while excersing and keeps your body toxin free. Also certain yoga pranayams increases your lung capacity,which are very helpful in COVID 19.It willhelpin making breathing hastle free especially for cronavirus patients.

5. Avoid habbits and addictions-

People addicted to alchohol,smoking and tobacco should avoid their habbits in these times, as these habbits decrease the body immunity and then you are more prone to infections. Also, we all know these addictions are not very healthy in normal time too.

6. Meditation-

Meditation releases the dopamine hormone in your body which keeps you relaxed and stress free.Low levels of dopamine may negatively affect your mood resulting you in stress which again leads to low immunity.So keep your mind and body relaxed and let your parasympathetic system work ( system of rest and digest, a brake after a danger has passed )more than your sympathetic system, which causes a state of (fight or flight, respond to dangers with burst to bodies energy). Adrenaline or also called Epinephrine, this hormone is a crucial part of the body's fight-or-flight response, but over-exposure can be damaging to health. Adrenaline is produced in the medulla in the adrenal glands as well as some of the central nervous system's neurons. This hormone is released in body when a person is under stress or a state of flight and flight, which when released in excess amounts damages health. So practice meditation every day.

7. Positive thinking, balanced life-

Thinking positive leads to secretion to lot of chemicals in your brain which are natural immunity boosters. Thinking right, with balanced work life and zero stress.

CONCLUSION:

COVID-19 is just a phase and will pass by with evolving vaccines coming up already undergoing trials. But effective management of corona virus comprises of all the medications, therapies as well the 7-pointer lifestyle mentioned. Every step and in combination plays a crucial role in treating patients with corona virus. Till date 5.51 million people have recovered worldwide and 24.3million have recovered in India. This battle shall end soon with emerging vaccines coming up. Without vaccines also the treatment results are promising against this pandemic. Also seen people with good immunity are not at all getting exposed to the virus on exposure, due to healthy living.

REFFERENCES:

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Received on 05.10.2020 Revised on 30.10.2020

Asian J. Pharm. Res. 2020; 10(4):327-330.

DOI: 10.5958/2231-5691.2020.00056.8