INTRODUCTION:

By the December 2019, an epidemics of infectious disease, named as novel coronavirus, emerged in the seafood market of Wuhan city of China.In the following weeks, this severe virus infection has spread across more than 183 countries in the world.¹In the last two decades, novel coronavirus has emerged as the third serious outbreak after the SARS-CoV (in 2002) and MERS-CoV.²Following the outbreak, public health, scientific and clinical organization of China immediately recognized the structure of this new virus and shared the information with the WHO about the genomic sequence of virus.³Based on its genetic sequencing, it is likely to be originated from bats and spread to humans from an unknown mammals host.⁴World health organization has declared the outbreak of coronavirus as Public Health Emergency of International Concern (PHEIC) on January 30, 2020.⁵Further, on February 12, WHO designated the novel coronavirus disease as COVID-19.⁶

COVID-19, a fetal contagious disease, majorly effect the respiratory, neurological, hepatic and enteric system of human.⁷Coronaviruses, RNA enveloped viruses, belonging to the coronaviridae family, induces the COVID-19 disease in humans and wildlife.⁸Fever, cough, running nose, breathing difficulties are the most prominent symptoms occur in patients suffering from COVID-19.^9,10Final confirmation of the disease is done with real time-transcription polymerase chain reaction(RT-PCR).¹¹

Epidemiology:

China is considered as zoonotic region of COVID-19 infection as first case of active COVID-19 infection was reported in Wuhan city of China in 17 November as according to media reports of China.¹²Between 18 December to 29 December, five patients having problem of respiratory distress syndrome were hospitalized, out of which one of the patient was died. By January 2, 2020 41 patients had been diagnosed as confirmed cases of COVID-19 infection.¹³From January 2 to 22 January, there is exponential rise in the cases from 41 to 571 in 25 cities of China. Another report submit by the China Health Commission on 25 January report the total 1975 confirmed cases with total death of 56 deaths.¹⁴By the end of January 30, 90 cases of COVID-19 was reported on Taiwan, Thailand, Vietnam, Malaysia, Nepal, Sri Lanka, Cambodia, Japan, Singapore, Republic of Korea, United Arab Emirates, United States, The Philippines, India, Australia, Canada, Finland, France, and Germany.¹⁵

Age factor, a major risk factor of incidence of COVID-19.¹⁶The distribution of cases of COVID-19 according to age wise as tabulated in table 1

Table1: Age distribution of identified COVID-19

Age (Years)	Percentage
More than 80	3%
30-79	87%
20-29	8%
10-19	1%
Less than 10	<1 %

According to the Coronavirus disease 2019 (COVID-19) Situation Report– 120 by WHO, as of 19 May 2020 as shown in fig 1:

Fig 1: Graphical Representation of Covid-19 statistics by WHO data

Structure:

Recent studies by cryo-electronmicroscopy and cryo-elctrontomography suggested that coronoviruses are spherical to pleomorphic enveloped particles having a single-strand of positive sense RNA.^17,18 Club shape spike projections originating from the surface of the coronavirus virion is most prominent and defining feature of the coronavirus virion. Mainly four structural proteins are present in the coronavirus structure- spike (S), membrane (M), envelope (E), and nucleocapsid (N) proteins.^19,20In most of the coronaviruses, furin like protease enzymes cleaves the S protein into two different polypeptides- S1 and S2 where S1 represent the receptor binding domain of S protein.^21,22Most abundant protein present in the coronavirus virion is the M protein which exists in the form of dimer. M protein of the virionmay exist in two different conformation which increase the potential of coronavirus to bind with the nucleocapsid.²³E protein present in lower quantities within the virus and it play a role in the assembly and release of the virus. Only protein present in the nucleocapsid of coronavirus virion is the N protein.²⁴The structure of the coronavirus is represented as follows in fig 2:²⁵

Fig 2: Proposed structure of coronavirus

Virus Replication and life cycle:

Corona virus life cycle can be majorly divided into the four interlinked stages (1) Binding and Entry (2) Expression of Replicase protein (3) Replication and transcription (4) Assembly and Release.²⁶ In the first stage, virus attached with the ACE2 receptors on the host cell body by utilizing receptor binding domains present on its S protein.^27,28Strength of S protein-receptor interaction contribute to the virus potential to induce the infection in host body.In the next stage, protease enzyme cathepsin mediate the S protein proteolytic cleavage by which virus get enter into the cytosol of host body. After binding and making entry into cytosol, next stage is followed by RNA replicase gene translation.²⁹ For the expression of two major polyproteins, a slippery sequence (5′-UUUAAAC-3′) is used by the virus which ultimately encodes its two replicase genes large ORFs, rep1a and rep1b.^30,31Following the replicase genes expression, both genomic and sub genomic RNA production occur through the negative strand intermediates.^32,33 In the next step, translation and entry of S, E and M protein into the endoplasmic reticulum occur. Further, the movement of these proteins occursinto the golgi-endoplasmic reticulum intermediate compartment by the secretory pathways. Following the assembly of the proteins present on the virus structure, virion transportation across the vesicle occur and by the exocytosis, virion releases its proteins.³⁴

Symptoms and clinical Features:

COVID-19 is a disease characterized by range of symptoms from asymptomatic patients to multiorgan failure and septicaemia.³⁵2-14 days is the incubation period of coronavirus infection with 5-6 days is the median period.³⁶Symptoms such as fever, cough, headache, diarrhoea and dyspnoea develop in most of the patients suffering from COVID-19.³⁷Further, certain symptoms like fever, dry cough are also occur in patients suffering from betacoronavirus however upper respiratory symptoms like sneezing, sore throat, rhinorrhea helps in differential diagnosis between coronavirus and betacoronavirus infection.^38,39Various factors may contribute to increase severity of disease such as weak immune system of patients, presence of other pre-existing diseases such as diabetes, hypertension, cirrhosis and Parkinson. Radiological screening of patients died from COVID-19 represents the various abnormal physiological changes like acute cardiac injury, acute respiratory syndrome and peripheral ground glass opacities in both of the lungs.⁴⁰Depending upon the severity, clinical features of COVID-19 diseases are divided into three categories as shown in table 2:⁴¹

Table2: Categorization of clinical features of COVID-19 based on severity

S. No	Severity	% of cases	Clinical Features
1	Mild	81%	Mild pneumonia and non-pneumonia
2	Severe	14%	Dyspnea, blood oxygen saturation
3	Critical	5%	Respiratory failure, Multiple organ dysfunctioning, septic shock

IntraspeciesTransmission:

Various wild and domestic animals such as camels, bats and cats act as reservoir of corona viruses. Before the epidemics of COVID-19 infections it is suggested that occurrence of animal coronavirus among human is very less.⁴²However, first case of COVID-19 reported in Seafood Market in Wuhan, China suggested about the animal to person transmission of coronavirus. After reporting of this case, it was suspected that either the consumption of infected host animals or direct contact with animals was the main route of SARS-CoV transmission. Further, cases reported among medical staff and others person having no history of contact with the host animals provides evidence of human-to human transmission. Family members, medical staff, who are in direct contact with patients, are at the major risk of getting infected.⁴³ Health authorities of China suggested about the guidelines of the major three routes of transmission for the COVID-19: (1)aerosol transmission (2) contact transmission (3) droplet transmission.⁴⁴Aerosols are produced in the environment when the respiratory droplets produced by infected patients by coughing or sneezing mix into the air.⁴⁵Further, contact transmission was reported to occur if the health individual touches the virus contaminated objects, after that when they subsequently touch their mouth and nose with contaminated hands.Coughing or sneezing by the infected individual contribute to the droplet transmission for the COVID-19. Droplet transmission occurs when person in close contact with the infected person ingested or inhaled the respiratory droplet produced by the infected patient.⁴⁶

Pathogenesis and diagnosis:

Entry of virus in the body stimulates its binding with ACE-2 enzymes present on cell membrane of body cells including respiratory tract. Binding stimulate the ACE-2 expression that tightens the cell binding and entry of virus inside the cell.^47-49ACE-2 expression alters the immune response by altering the levels of proinflammatory and anti-inflammatory cytokines.⁵⁰The result is significant increase in leukocyte number, proinflammatory cytokines such as interleukins, TNFα. Due to which abnormal findings in the lower respiratory tract are seen in virus infected patients that may cause pneumonia and Multiorgan failure.⁵¹To investigate the presence of virus in host body RT-PCR is suggested as a powerful diagnostic tool. This technique confirmed the presence of positive nucleic acid of COVID-19 in sputum, swabs and secretions of lower respiratory tract.⁵²Abnormal laboratory findings include elevated neutrophil count, LDH, aspartate aminotransferase, alanine transferase, creatinine, bilirubin, procalcitonin, c-reactive protein and reduce the amount of lymphocyte and albumin.⁵³

Treatment and Preventive strategies:

Current strategies:

Due to the lack of any recommended specific antiviral treatment against COVID-19 and unavalibity of any vaccine, current treatment strategies focused on the symptomatic treatment of COVID-19.⁵⁴Oxygen therapy is recommended as the major treatment strategies in the patients with severe COVID-19 infection and extracorporeal membrane oxygenation (ECMO) is also approved by WHO for the patients with the refractory hypoxemia.⁵⁵

Various antiviral drugs such as neuroaminidase inhibitors (oseltamivir, peramivir, zanamivir, etc) and systemic corticosteroids are not approved by US-FDA for the treatment of COVID-19.⁵⁶Remdesivir, broad spectrum antiviral drug, interfere with the NSP12 polymerase is helpful in the successful treatment of first COVID-19 patient in US.⁵⁷Choroquinine an antimalarial drug is a repurposed drug having strong potential to treat COVID-19 patients. The underlying mechanism of its effectiveness against viral infections is not well understood. Various mechanisms are purposed: Choroquinine can exhibit potent effect against SARS-Co by suppressing its pH dependant replication, inhibiting the production of TNF-α and IL-6.⁵⁸Various studies also suggested that it can also inhibit the glycosylation of SARS-CoV receptors. Combination of the both the drugs chloroquine and remdesivir was proven to be effective against the emerged SARS-Cov-2 in vitro.⁵⁹

COVID-19 is severe contagious diseases in which the patient infected with the disease is the main infection source. To control the outbreak of COVID-19 infection, extensive measures are required to be taken to reduce the person to person transmission.⁶⁰Isolation of patients infected with the COVID-19 is the need of hour.⁶¹Further, specialattention should be given to the children, elderly people and health care workers who are more suspectible to get infected. The public services and facilities should provide decontaminating reagents for cleaning hands on a routine basis.⁶²WHO also recommend the various guidelines to reduce the spread of COVID-19 such as frequent washing of hands with the alcohol-based sanitizer, avoid the close contact with the person having symptoms like coughing and sneezing, maintain social distancing and usage of flexed elbow to covering the mouth and nose during coughing and sneezing.⁶³

CONCLUSION AND FUTURE DIRECTIONS:

In the past few years, the emergence of various human and veterinary diseases by different species of corona viruses has occurred. It is likely to believe that these viruses will continue to cause severe diseases in human and animals due to its strong capability to divide and to mutate. Worldwide outbreak of COVID-19 is still ongoing. COVID-19 is highly transmissible disease however its mortality rate is less compared to SARS (severe acute respiratory syndrome) and MARS (middle east respiratory syndrome), previous outbreak of coronavirus. New insights into the pathogenesis, clinical features, transmission are still developing. At present, there is no any vaccine developed against corona virus. However, some therapies such as oxygen therapy, refractory hypoxemia support the symptomatic treatment of patients. Various preventive measures social distancing, avoiding contact with the infected patients as much as possible can be done to prevent COVID-19 as per the guidelines issued by WHO and EDC. Appropriate co-ordination have shown by the National and International health care agencies to handle the outbreak of COVID-19. Further, future research and cooperation at the International level is the need of hour to reduce the outbreak of COVID-19. Finally, characterization of pathogenesis mechanism of coronaviruses and understanding the immunopathological response of host body will significantly helps the scientist improve design vaccines against coronavirus and reduce disease burden.

CONFLICT OF INTEREST:

There is no conflict of Interest.

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Received on 31.05.2020 Modified on 21.06.2020

Res. J. Pharmacology and Pharmacodynamics.2020; 12(3):111-116.

DOI: 10.5958/2321-5836.2020.00021.X