INTRODUCTION:

Outbreak of novel Corona Virus Disease popularly known as COVID-19 in 2019 at Wuhan, China has affected all sectors of the economy. It has put the scientists and researchers on the run since the naming and declaration of this disease as pandemic, Every day, since the outbreak of this pandemic, several humans lost their lives and means of livelihood to this new strain of virus⁽¹⁾. The modes of transmission of this COVID-19 aided the rapid spread of this pandemic. COVID-19 enters human body through the all the major openings of the body and depends on cellular proteases that help to split and establish further penetration. The disease already affected over half a million people lives, mostly the aged. Many local and international researchers are funded huge in order to produce vaccine and drugs that will treat this disease⁽²⁾.

Corona virus

· The first outbreak of COVID-19 was reported in Wuhan, China, in December 2019.

· The name "coronavirus" is derived from Latin word corona, meaning "crown" It is having crown like projections on its surface.

· It was declared by the World Health Organization the outbreak a Public Health Emergency of International Concern on January 30, 2020 and a pandemic on March 11, 2020⁽⁶⁾.

· In India first confirmed positive case was reported in January 30^th, in Kerala state.

· Total Nation is declared as Janatha Curfew on March 22^nd, 2020.

· Total 21 days of national wide lock down is imposed form March 25^th to May 31^st 2020.

· Now unlock phase is going on.

So many countries in the world are working to flat the curve of incidence of COVID-19cases, As the curve is becoming flat it indicates the reduction of no cases of COVID-19 pandemic.

Corona virus is having crown-like spike on its outer surface thus it was named as corona virus. At the end of 2019, Wuhan, an emerging business hub of china experienced an outbreak of a novel corona virus which belongs to β group of corona viruses. The transmission rate of SARS-CoV-2 is higher than SARS-CoV and the reason could be genetic recombination at S protein in the RBD (Recent Binding Domain) region of SARS-COV-2 may have enhanced its ability of transmission⁽³⁾.

It shows flu-like symptoms like fever, cough, cold etc. Although serious lung injury has been reported at all ages, high-risk in old people, the virus is more likely to cause extreme intestinal pneumonia, acute respiratory distress syndrome (ARDS) and resulting multiorgan failure, which are liable for serious acute respiratory failure and death⁽⁴⁾.

Epidemiology

In December 12, 2019 Wuhan city sea food market as the starting point for accounting numerous viral Pneumonia cases and were officially reported on last date of December 2019.Coronaviruses are phylogenetically close to SARS-CoV-2 have been detected in pangolins (scaly anteaters), especially in Malayan pangolins (Sunda pangolins) in China, which are located throughout Southeast Asia, is now considered to be a potential intermediate host of SARS-CoV-2.This new virus and disease were unknown before the outbreak began in Wuhan, China, in December 2019. COVID-19 is now a pandemic affecting many countries globally⁽⁵⁾.

Most people (about 80%) recover from the disease without needing hospital treatment. Around 1 out of every 5 people who gets COVID-19 becomes seriously ill and develops difficulty in breathing. Older people, and those with underlying medical problems like high blood pressure, heart and lung problems, diabetes, or cancer, are at higher risk of developing serious illness⁽⁶⁾.

Females are more prone to incidence of COVID-19 as compared to males because of the presence of Estrogen hormone, having capability to prevent the penetration of corona virus. Some reports have shown that asymptomatic people can also transmit the virus ⁽⁰⁷⁾.

Practicing hand and respiratory hygiene is always important and is the best way to protect others and yourself⁽⁰⁸⁾.

Transmission

People can get infection with COVID-19 from the infected source. It spreads primarily from person to person through small water droplets from the nose or mouth, which are expelled when an infected person coughs, sneezes, or speaks. These droplets are relatively heavy, do not travel far and quickly sink to the ground. Therefore, it is important to stay at least 1 meter away from others. These droplets can land on objects and surfaces around the person. Many people with COVID-19 having only mild symptoms in the early stages of the disease. People can become infected by touching these objects or surfaces, then touching their eyes, nose, or mouth. Therefore, it is important to wash your hands regularly with soap and water or clean with 60 % alcohol-based hand wash⁽⁰⁹⁾

Important Definitions

· Quarantine means restricting activities or separating people who are not infected themselves but may have been exposed to COVID-19. The goal is to prevent spread of the disease at the time when people just develop symptoms (14)

· Isolation means separating people who are ill with symptoms of COVID-19 and may be infectious to prevent the spread of the disease.

· Physical distancing means being physically apart. WHO recommends keeping at least 1-metre distance from others. This is a general measure that everyone should take.

· Self-quarantine means to separate yourself from others because you have been exposed to someone with COVID-19 even though you, yourself, do not have symptoms. During self-quarantine you monitor yourself for symptoms. The goal of the self-quarantine is to prevent transmission⁽¹⁰⁾.

Preventive Measures

The most effective ways to protect ourself and others against COVID-19 are to:

· Frequently and thoroughly clean our hands with an alcohol-based hand sanitiser or wash with soap and water for at least 20 seconds or using 60% alcohol-based hand rub kills viruses present on our hands.

· Maintain at least 1 metre distance between person to person. When someone coughs, sneezes, or speaks they spill small liquid droplets from their nose or mouth which may contain virus.

· Avoid going to crowded places, Where, it is more difficult to maintain physical distance of 1 metre.

· Avoid touching eyes, nose and mouth. Hands touch many surfaces and can pick up many microbes. Once contaminated, hands can transfer the virus to your eyes, nose or mouth. From there, the virus can enter your body and infect us⁽¹¹⁾.

· Maintain good respiratory hygiene by covering mouth and nose with our bent elbow or tissue when you cough or sneeze, dispose the used masks immediately and wash your hands. By following good respiratory hygiene, we can protect the people around us from viruses such as cold, flu and COVID-19.

· Frequently wipe your cell phones i.e. screen with liquor-based disinfectant.

· Don’t split in public.

· Immune compromised patients should avoid public exposure and public gatherings. Strict personal hygiene measures are necessary for the prevention and control of the infection.

· Keep up to date on the latest information from trusted sources, such as W.H.O or your local and national health authorities ⁽¹²⁾

Some western, traditional, or home remedies may provide comfort and alleviate symptoms of mild COVID-19, there are no medicines that have been shown to prevent or cure the disease. WHO does not recommend self-medication with any medicines, including antibiotics, as a prevention or cure for COVID-19. However, there are several ongoing clinical trials of both western and traditional medicines. WHO is coordinating efforts to develop vaccines and medicines to prevent and treat COVID-19 and will continue to provide updated information as soon research results become available⁽¹³⁾.

Corona virus on surfaces can easily be cleaned with common household disinfectants that will kill the virus. Studies have shown that the COVID-19 virus can survive for up to 72 hours on plastic and stainless steel, less than 4 hours on copper and less than 24 hours on cardboard.

Antibiotics do not act against viruses; they only act against bacterial infections. COVID-19 is caused by a virus, so antibiotics do not act on it. Antibiotics should not be used as a means of prevention or treatment of COVID-19. In hospitals physicians will sometimes use antibiotics to prevent or treat secondary bacterial infections which can be a complication of COVID-19 in severely ill patients. They should only be used as directed by a physician to treat a bacterial infection⁽¹⁴⁾.

The time period between exposure to COVID-19 and exposure of symptoms is around five to six days but can range from 1 – 14 days.

Structure of coronavirus

Nucleocapsid Protein (N): Its function is bound to RNA genome to make up Nucleocapsid.

Spike Protein (S): Its function is Critical for binding of host cell receptors to facilitate entry of host cell.

Envelope Protein (E): Interacts with Membrane protein to form Viral envelope.

Membrane Protein (M): Central organizer of CoV assembly determines shape of viral envelope⁽¹⁵⁾

Diagnostic Tests

The diagnostic tests for the identification of COVID-19 are the following:

· Real time reverse transcription polymerase chain reaction (RT-PCR)

· Loop-mediated isothermal amplification (LAMP)

· Lateral flow/Colloidal Gold Immune chromatography

Reverse-transcription polymerase chain reaction (RT-PCR):

Polymerase chain reaction is a very common scientific technique that has been widely used in medicine and research for around many years to detect genetical information. RT-PCR is a special technique used when RNA is being detected and now used to detect SARS CoV- 2, the virus causing COVID-19. This test frequently been used as a frontline test for COVID-19 as it directly detects for the presence of the virus RNA. RT-PCR tests are sensitive, quick, and reliable, capable of giving results in 3 - 4 hours.

Loop-mediated isothermal amplification (LAMP):

Loop-mediated Isothermal Amplification (LAMP) is identical process toRT-PCR. LAMP is conducted at a constant temperature of 60 - 65°C where as RT-PCR works at a series of temp changes to generate viral DNA copies. In LAMP the amount of DNA produced is higher than RT-PCR and the positive result can be seen directly without the aid of any machine. LAMP is a simple novel technique to perform for the identification of COVID-19.

Lateral flow/Colloidal gold immunochromatography:

Lateral flow assays are used to detect antibodies in diseased individual blood indicating that the patient has COVID-19 or has recovered from COVID-19. A drop of blood is taken from patient vein or from small finger by prick for the detection of immune antibody response to the virus instead of finding virus itself.The advantage of this technique is to find out whether the person is currently infected or fully recovered from COVID-19.

Life cycle of Corona Virus

1. Viral replication involves six steps: Attachment, Penetration, Uncoating, Replication, Assembly and Release.

2. During attachment and penetration, the virus attaches itself to a host cell and injects its genetic material into it.

3. During Uncoating, replication, and assembly, the viral RNA incorporates itself into the host cell’s genetic material and induces it to replicate the viral genome.

4. During release, the newly-created viruses are released from the host cell, either by causing the cell to break apart, waiting for the cell to die, or by budding off through the cell membrane.

Treatment

World Health Organisation declared the condition as Pandemic till now no drug is shown to be effective against the new virus SARS – CoV 2. Vaccines save millions of lives each year. Vaccines work by preparing our body’s natural defences - the immune system--- to recognize and fight against viruses and bacteria. If the body is exposed to those disease-causing pathogens again, then body immediately identify and destroy them, preventing illness. At present there is no treatment specifically approved for COVID-19, and no cure for an infection, no medication is recommended to treat COVID-19, although treatments and vaccines are currently under research. Antibiotics are not effective against viral infections such as COVID-19⁽¹⁶⁾.The FDA has granted the emergency use of antiviral drug Remdesivir and convalescent plasma therapy to treat COVID-19. The U.S. National Institutes of Health recently recommended the corticosteroid Dexamethasone for severe COVID-19 patients who require supplemental oxygen or mechanical ventilation. Convalescent plasma is blood donated by the recovered COVID-19 patients to treat people who are ill with COVID-19 in the hospital.Remdesivir got emergency use authorization (EUA) from the FDA on May 1, 2020, based on preliminary data showing a faster time to recovery of hospitalized patients with severe disease⁽¹⁷⁾.

Drugs used in the treatment

Favipiravir

It is an antiviral drug taken orally which was approved in Japan for influenza infection in 2014 and also for treatment of Ebola virus infection. Its mode of action is by direct inhibition of viral replication and transcription through misincorporation in nascent vRNA (viral ribonucleic acid), or by binding to RNA-dependent RNA polymerase enzyme preventing incorporation of nucleotides for vRNA replication and transcription⁽¹⁸⁾. Favipiravir has given approval by the National Health Commission of the People's Republic of China against the SARSCoV- 2 virus. Inorder to consider this drug for the treatment of COVID-19 more clinical data is required ⁽²²⁾

Chloroquine

Chloroquine is used for the prophylaxis and treatment of malaria, extraintestinalamebiasis and rheumatic diseases, treatment and prophylaxis of Zikavirus.As per the Emergency Use Authorization (EUA) of US FDA for the unapproved use of this drug in COVID-19 patients^(19,20). Chloroquine and hydroxychloroquine interfere with the entry of virus and interfering with terminal glycosylation of ACE2 receptors, translation, proteolysis, and replication.⁽²³⁾

Remdesivir

Remdesivir, is an ATP analog, used for the treatment of Ebola and coronavirus infections. It acts by inhibiting RNA-dependent RNA polymerase an imp viral enzyme, so that viral replication is inhibited. Food and Drug Administration (FDA) ordered the EUA on May 1^st2020 for the emergency use of Remdesivir for the treatment of COVID-19 patients in hospitals based on the preclinical data and clinical trials report^{(19, 20)}.

Lopinavir-ritonavir

Lopinavir and Ritonavir are the antiretroviral drugs which inhibit protease enzyme, used for the treatment of HIV-AIDS. Ritonavir retards the metabolism of Lopinavir and enhances the biological half-life and its antiviral activity. The Government of India Ministry of Health and Family Welfare Directorate General of Health Services (EMR Division) has recommended this drug combination for the clinical management of COVID - 19 in the following dosing schedule.

· Lopinavir 200 mg / ritonavir 50 mg 2 tablets twice daily,

· Lopinavir 400 mg / ritonavir 100mg / 5 ml, 5ml suspension twice daily, (if the patient is unable to take orally) for 14 days or for 7 days after becoming asymptomatic

Ribavirin

Ribavirin, a guanosineanaloguehaving broad spectrum activity against both type of viruses, used for the treatment of severe respiratory syncytial virus (RSV) infection in children, Lassa fever, influenza A and B. It inhibits viral replication by incorporating into viral RNA and inhibits RNA dependent RNA polymerase activity.

Ivermectin, Nitazoxanide

Ivermectin is a broad spectrum anti parasitic and Nitazoxanide is a first line antiviral drug having broad spectrum activity used for the treatment of COVID-19. It acts by inhibiting N protein expression of the virus⁽²¹⁾.

Currently all the countries are following three strategies in the development of drugs to treat the deadly virus

· Repurposing of existed antiviral drugs.

· Studying the properties of targeted drugs from chemical libraries by screening method

· Discovery and development of the new drug molecules although it is a challenging strategy; it takes around 12 – 14 years to develop one promising molecule.

Different drugs are having different properties and they act in a different way to treat Corona virus. Till now no drug is confirmed for the treatment of COVID-19, the use of single drug is not enough to control the deadly virus, so that combination of different anti viral drugs with different mechanisms are more effective⁽²³⁾.

AUTHOR CONTRIBUTION

All authors are equally contributed in data collection, review, and preparation of this manuscript and approved the final version for the publication.

CONFLICT OF INTEREST:

No conflicts of interest.

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Received on 13.05.2021 Modified on 10.08.2021

Asian J. Pharm. Res. 2021; 11(4):242-246.

DOI: 10.52711/2231-5691.2021.00042