INTRODUCTION:

The World Health Organisation (WHO) has declared the coronavirus disease 2019 (COVID-19) a pandemic. A global coordinated effort is needed to stop the further spread of the virus. A pandemic is defined as “occurring over a wide geographic area and affecting an exceptionally high proportion of the population.” The last pandamic reported in the world was the H1N1 flu pandemic in 2009.

On 31 December 2019, a cluster of cases of pneumonia of unknown cause, in the city of Wuhan, Hubei province in China, was reported to the World Health Organisation. In January 2020, a previously unknown new virus was identified, subsequently named the 2019 novel coronavirus, and samples obtained from cases and analysis of the virus’ genetics indicated that this was the cause of the outbreak. This novel coronavirus was named Coronavirus Disease 2019 (COVID-19) by WHO in February 2020. The virus is referred to as SARS-CoV-2 and the associated disease is COVID-19.

As of 15 May 2020, over 4,444,670 cases have been identified globally in 188 countries with a total of over 302,493 fatalities. Also 1,588,858 were recovered.

Coronaviruses are a family of viruses that cause illness such as respiratory diseases or gastrointestinal diseases. Respiratory diseases can range from the common cold to more severe diseases eg

· Middle East Respiratory Syndrome (MERS-CoV)

· Severe Acute Respiratory Syndrome (SARS-CoV)

A novel coronavirus (nCoV) is a new strain that has not been identified in humans previously. Once scientists determine exactly what coronavirus it is, they give it a name (as in the case of COVID-19, the virus causing it is SARS-CoV-2).

Coronaviruses got their name from the way that they look under a microscope. The virus consists of a core of genetic material surrounded by an envelope with protein spikes. This gives it the appearance of a crown. The word Corona means “crown” in Latin.

Coronaviruses are zoonotic, meaning that the viruses are transmitted between animals and humans. It has been determined that MERS-CoV was transmitted from dromedary camels to humans and SARS-CoV from civet cats to human. The source of the SARS-CoV-2 (COVID-19) is yet to be determined, but investigations are ongoing to identify the zoonotic source to the outbreak.

Causative agent: severe acute respiratory syndrome-coronavirus-2

The SARS-cov2 is a beta coronavirus belonging to family-friendly coronaviridae. metabgenomic sequencing of RNA samples isolated from bronchoalveolar lavage fluid patients suffering from severe acute respiratory illness.in the city of Wuhan identified a novel virus as causative pathogen. till now 11 complete genome sequences isolated from China and five of which are isolated in Japan. these showed more than 99 percent identity. this encodes polyprotein, surface glycoprotein, membrane glycoproteins, nucleocapsid phosphoproteins.

The orf1ab polyprotein encoded by the genome of SARS Cov 2 isolated from Japan patients. has 24 nucleotide delation. genome delation in the japanese SARS-COV 2 virus was observed as the UTR locus and extreme 3' end of the genome. phylogenetic analysis using complete genome sequence of SARS Cov 2 revealed that it's genome sequence are very similar (90%) to SARS Covs. analysis of receptor binding domains suggest that SARS Cov 2 possibly use angiotensin converting enzyme 2 (ACE-2) as a cell receptor to infect the host.

Life cycle of covid-19-

Life cycle of coronavirus takes place in following steps:

1. Attachment and entry

2. 2)Replicase protein expression

3. Replication and transcription

4. assembly and release

1. Attachment and entry:

The attachment of virion to host cell takes place by interaction between and S protein and it's receptor.it is first determinant to infect the host and also governs the tissue tropism of virus. generally these viruses utilizes peptidase as their cellular receptor. the sites of receptor binding domains (RBD)within the S1 region of coronavirus s protein vary depending on virus. with some having RBD at the N-terminus of S1(MHV), while others SARS Cov-2 having RBD at C-terminus of S1. Many alpha coronaviruses utilize aminopeptidase as their receptor, MERS-coV binds to dipeptidyl peptidase 4, SARS-cov2 use ACE-2 as receptor. after this receptor binding virus gain access to host cell cytosol following by the fusion of viral and cellular membrane by cleavage of S protein through cathepsin. then fusion forms six helix bundle and ultimately release of viral genome into cytoplasm.

2. Replicase protein expression:

In this step the translation of Replicase gene from the virion genomic RNA takes place that encodes two large ORFs rep1a and rep1b that express pp1 a and pp1b polyproteins by utilizing a slippery sequence(5'-UUUAAAC-3') and RNA pseudoknot that causes ribosomal frameshifting from rep1a reading frame to rep1b ORF. Rivonucleases nsp15-NendoU and nsp-14activities are unique to the Nidovirales order and considered genetic marker for Corona virus.

3. Replication and transcription:

Viral RNA synthesis produces not genomic and sub-genomic RNAs. the novel aspect of coronavirus replication is how leader and body TRS segment fuse during production of sub- genomic RNAs.it is believed that this occur during discontinuous extension of negative strand RNAs. finally coronaviruses has ability to recombine through both homologous and heterologous recombination. virus recombine is tied to strand switching ability of the RdRp. recombination causes the evolution of virus, and is the basis of targeted RNA recombination. abreverse genetic tool used to engineer viral recombinants at the 3' end of the genome.

4. Assembly and release:

Following replication and sub-genomic RNA synthesis the viral structural proteins E, M and S are translated and inserted into endoplasmic reticulum. this then moves towards the endoplasmic reticulum-Golgi intermediate compartment (ERGIC). where viral genomes encapsidated by N proteins forming mature virions. M protein directs the most protein- protein interaction for coronaviruses. but it is only not sufficient for virion formation, when M protein is expressed along E protein virus like particles are formed (VLPs) and this two proteins together forms Corona virus envelope. N protein increases VLPs formation and E and M proteins help in maturing virion envelope. Following assembly virion are transported to cell surface in vesicles and released by exocytosis.in several Corona viruses S protein that does not get assembles into virions transits to cell surface where it mediate cell- cell fusion between infected cell and adjacent uninfected cell. this leads to formation of multinucleated cells which allows the virus to spread within an infected organism without getting detected or neutralised by virus specific antibodies.

Clinical Presentation:

Typically, Coronaviruses present with respiratory symptoms. Among those who will become infected, some will show no symptoms. Those who do develop symptoms may have a mild to moderate, but self-limiting disease with symptoms similar to the seasonal flu. Symptoms may include:

· Respiratory symptoms

· Fever

· Cough

· Shortness of breath

· Breathing difficulties

· Fatigue

· Sore throat

A minority group of people will present with more severe symptoms and will need to be hospitalised, most often with pnemonia, and in some instances, the illness can include ARDS, sepsis and septic shock. Emergency warning signs where immediate medical attention should be sought include:

· Difficulty breathing or shortness of breath

· Persistent pain or pressure in the chest

· New confusion or inability to arouse

· Bluish lips or face

High-Risk Populations:

The virus that causes COVID-19 infects people of all ages. However, evidence to date suggests that two groups of people are at a higher risk of getting severe COVID-19 disease:

· Older people over 70 years of age

· People with serious chronic illnesses such as:

· Diabetes

· Cariovascular disease

· Chronic respiratory disease

· Cancer

· Hypertension

· Cronic liver disease

The WHO has issued and published advice for these high-risk groups and community support. This is to ensure that these high-risk populations are protected from COVID-19 without being isolated, stigmatized, left in positions of increased vulnerability or unable to have access to basic provisions and social care.

WHO advice for high-risk populations:

· When having visitors at your home, extend “1-meter greetings”, like a wave, nod or bow.

· Request that visitors and those who live with you, wash their hands.

· Clean and disinfect surfaces in your home (especially those that people touch a lot) on a regular basis.

· Limit shared spaces if someone you live with is not feeling well (especially with possible COVID-19 symptoms).

· If you show signs and symptoms of COVID-19 illness, contact your healthcare provider by telephone, before visiting your healthcare facility.

· Have an action plan in preparation for an outbreak of COVID-19 in your community.

· When you are in public, practice the same preventative guidelines as you would at home.

· Keep updated on COVID-19 through obtaining information from reliable sources.

Transmission of COVID-19:

Evidence is still emerging, but current information is indicating that human-to-human transmission is occurring. The routes of transmission of COVID-19 remains unclear at present, but evidence from other coronaviruses and respiratory diseases indicates that the disease may spread through large respiratory droplets and direct or indirect contact with infected secretions.

The incubation period of COVID-19 is currently understood to be between 2 to 14 days. This means that if a person remains well after 14 days after being in contact with a person with confirmed COVID-19, they are not infected.

Human Coronavirus Types:

Coronaviruses are named for the crown-like spikes on their surface. There are four main sub-groupings of coronaviruses, known as alpha, beta, gamma, and delta.

Human coronaviruses were first identified in the mid-1960s. The seven coronaviruses that can infect people are:

Common human coronaviruses

1. 229E (alpha coronavirus)

2. NL63 (alpha coronavirus)

3. OC43 (beta coronavirus)

4. HKU1 (beta coronavirus)

Other human coronaviruses:

5. MERS-CoV (the beta coronavirus that causes Middle East Respiratory Syndrome, or MERS)

6. SARS-CoV (the beta coronavirus that causes severe acute respiratory syndrome, or SARS)

7. SARS-CoV (the novel coronavirus that causes coronavirus disease 2019, or COVID-19)

People around the world commonly get infected with human coronaviruses 229E, NL63, OC43, and HKU1.

Sometimes coronaviruses that infect animals can evolve and make people sick and become a new human coronavirus. Three recent examples of this are 2019-nCoV, SARS-CoV, and MERS-CoV.

DIAGNOSIS:

Preferred clinical samples are taken for confirmation of suspected cases in the laboratory. nasopharyngeal and oropharyngeal swabs collected using Dacron swabs, also expectorated sputum, Endotracheal aspirate and tissue.

The Clinical sample after collected, kept in sterile container with normal saline which covers the sample. In case of the serum samples, they are collected in pais, for the collection purpose red cap vials are used with the clot activators during both acute phase and convalescent phase of illness. The triple packaging of sample is recommended by the guidelines.

The swabs taken should be placed in a commercially available transport medium. It is necessary to collect information i.e. patients’ demographic details, site of collection, tests required for clinical history, symptoms, risk factors. This information is necessary and mentioned to minimize risks of transmission. UN3373 labelling must be done for category Biological substances sample packaging. BSL-3 laboratory and BSL-2 laboratory used for culture of the virus as recommended by WHO. For accuracy and minimizing risks of during diagnosis the specimen of SARS-COV-2 handling one must be ensure neither the sample nor HCW is contaminated.

The seroconversion of disease is seen by detection of antibody convalescent phase serum. Acute phase serum sample titers between the acute and convalescent phases. Direct or indirect fluorescent antibody test (IFA) are used for conformation of seroconversion.

PREVENTION OF TRANSMISSION:

Transmission of SARS-COV-2 done by respiratory droplets and physical contact. Certain measures are taken to prevent transmission. Sanitizers are used for hand washing, also alcohol-based hand rubs i.e. ABHRS containing 60-70% ethanol. Hand washing is necessary for prevention of transmission of COVID. Correct steps should be followed in hand washing using soaps and sufficient water. Disposable tissue papers should be preffered and disposable is done after use. We should avoid cloth towels for drying purposes. Transmission avoided by wearing the medical masks, goggles, gowns, gloves and shoe covers should be used to prevent transmission. Changing of suits and cloths should be done before and after visiting the patient areas. Highly hygiene is to be performed while dealing with the patients. Correct dispose of masks, gloves should be done.

Long sleeved, sterile water gowns made up of non-adsorbable water are to be worn. Water aprons should be used if gowns are not available. Mouth and nose covering should be done while sneezing and coughing. Disposable tissue paper should be used instead of cotton cloth. Care should be taken to avoid people with symptoms getting crowded in public areas. Care should be placed in a well-ventilated room.

TREATMENT OF COVID BY DRUG THERAPY:

Till the date there is no any permanent treatment on covid-19 discovered yet but some of this drugs are used to recover patients by symptomatic treatment and boosting immunity:

Hydroxychloroquine:

Category: Antimalarial.

What it does: found to inhibit the activity of SARS-COV2 in lab studies by decreasing the acidity in endosomes which are compartment inside cell that some viruses co-opt to enter the cell and cause infection.

When should it be used: prophylaxis for high risk close contacts, health workers and frontline workers, who had unprotected exposure to infection. It is not approved for severely ill patients.

Mode of delivery: oral tablets

Glucocorticoids:

Category: corticosteroids

What it does: Calms acute inflammatory response to slow disease progression by preventing the body from pumping out the inflammatory chemicals.

When should it be used: For severely ill patients with progressive deterioration of oxygenation indications, rapid worsening of imaging and cytokine storm?

Mode of delivery: intravenous

Convalescence plasma:

Category: plasma therapy

What it does: infection fighting antibodies from blood of recovered patients given to ill patients to boost their immunity.

When should it be used: for patients with moderate disease whose oxygen requirement is progressively increasing despite the use of steroids.

Mode of delivery: transfusion

Remdesivir:

Category: antiviral

What it does: speeds recovery by shutting down replication of virus in body. hospitalized patients given rendesivir discharge within 11 days on average compared to 15 days for patients on standard care.

When it should be used: given to hospitalized patients on oxygen with moderate covid-19.

Mode of delivery: intravenously in ICU. Gilead science working on inhaler.

*HIV drugs for Corona Virus Treatment*

For the treatment of MERS and SARS corona viruses Abbvie's HIV protease inhibitor, lopinavir is being studied along with ritonavir. The re purposed drug is already approved for the treatment of HIV infection under the trade name Kaletra.

*Lopinavir is demonstrated reduced mortality in non-human primates’ model of the MERS and it is believed to act on the intercellular processes of Coronavirus replication.

The antiviral drug Galidesivir has shown broad-spectrum activity against a wide range of pathogens including Coronavirus. The process of viral replication is disrupted as it is a nucleotide RNA polymerase inhibitor.

The drug has already shown survival benefits in patients against deadly viruses such as Ebola, Zika, Marburg, and Yellow fever. Galidesivir is currently in advanced devepment stage under the Animal rule to Combat multiple potential viral threats including Coronaviruses, flavivirus filo viruses, paramyxovirus, toga viruses, bunyaviruses, and arena viruses.

*Entos pharmaceuticals is developing Fusogenix DNA vaccine developed using the Fusogenix drug delivery platform is a proteo-lipid vehicle that introduces genetic play load directly into the cells. Entos is working on developing an optimisised payload containing multiple protein epitopes derived from SARS-COV-2 proteins, which will stimulate an immune response in the body to prevent COVID - 19 infections.

*The national medical products administration of China has approved the use of Flavilavir an anti-viral drug, as a treatment for Coronavirus. The drug has reportedly shown efficacy in treating the disease with minimal side effects in a clinical trial involving 70 patients.

*The US Food and Drug administration, (FDA) approved limited emergency use for chloroquine and hydroxy chloroquine as a treatment of COVID-19.

CONCLUSION:

The detail study of Corona virus is done by observing present pandemic situation in all over the world. Here the human Corona virus types and their severity is also studied and its lifecycle and transmission as well as preventive measures are explained and concluded. presently there is no permanent treatment on this but research work is going on from the route cause of disease. some of the drugs are mentioned above are approved all over the world to boost immunity and fight against Corona. And generally patients having better immunity are recovering at great manner.

REFERENCES:

1. Novel Coronavirus disease (COVID-19) pandemic: A review of current evidence

2. Translational Health Science and Technolog Institute, Pali Haryana, India

3. Indian Council of Medicinal Research, New Delhi

4. 4https://www.sciencemag. org/news/2020/02/bit-chaotic-christening

5. https://www.who.int/dg/speeches /detail-who-director

6. https://doi.org/10.1101/2020.02.07.937862

7. https://www.who.int/news-room/detail/30-01-2020-statement-on-the-second-meeting-of-the-international-health-regulaions-(2005) - emergency - committee-regarding - the-outbreak-of-novel-coronavirus-(2019)

8. https://www.centerforhealthsecurity.org/resources /COVID-19/200130-n

9. https://www.who.int/csr/resources/publications/biosafety/

10. https://www.japantimes.co.jp/news/2020 /02/13/national/coronavirus - diamond - princess/

Received on 23.08.2020 Modified on 12.09.2020

Research J. Science and Tech. 2020; 12(4):338-345.

DOI: 10.5958/2349-2988.2020.00051.0