SARS-Cov-2 The Beta Genome Coronavirus: A Brief Overview,

Pathogenesis and Treatment

 

Mr. Akshay Gade*, Miss. Rutuja Sawant, Miss. Shreya Parkar, Miss. Prajakta Kegade

Department of Pharmaceutics, M Pharmacy, University of Mumbai, Vidya Nagari, Kalina,

Santacruz East, Mumbai, Maharashtra 400098.

 

ABSTRACT:

Corona Virus Disease (COVID 19) causes respiratory illness outbreak in Wuhan, Hubei Province, China in December. The COVID 19 is caused by the SARS-CoV-2, it is highly infectious respiratory disease including pneumonia, cold, sneezing, and coughing while in the animal it causes diarrhea and upper respiratory diseases. Over the next few weeks, the virus spread from Wuhan to affect different provinces in China, and after a few months, it is now presenting in 109 countries and many more are included in the list with a higher number of patients. These patients having similar symptoms, but the level of infection is different from the patients. The symptoms of COVID 19 in patients mainly include initial cold, mild fever, sore throat with a dry cough, breathlessness, fatigue, malaise among others. Usually the elderly and those with comorbidity, the disease may progress to pneumonia, acute respiratory distress syndrome (ARDS), and multi-organ dysfunction. Most of the recently infected people are asymptomatic so it’s a very crucial challenge for the government to diagnose the patients with no symptoms but infected by this disease. The World Health Organization has declared it an International emergency which is the evidence statement that noticed every country to follow the new rules of emergency in their respective countries. Various prevention and treatment measures are followed by various countries to find a way to come out from this pandemic but still, no fully assessed treatment was found. Based on current published evidence, this review systematically summarizes the epidemiology, it's control and prevention. We conducted a literature review of publicly available information about the pathogen and the current epidemic, causative agent, pathogenesis, and immune responses, epidemiology, diagnosis, treatment, and management of the disease, strategies are all reviewed.

 

 

 

INTRODUCTION:

The 2019 novel corona virus (2019-nCoV) or the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) as it is rapidly spreading to the rest of the world from its origin in Wuhan City of Hubei Province of China¹.

 

The disease it causes has been named coronavirus disease 2019 (COVID-19). The SARS-CoV is a positive-stranded RNA virus that originates from the Coronaviridae family. Other viruses from the same family include the severe acute respiratory syndrome coronavirus (SARS-CoV), which appeared in 2002, and Middle East respiratory syndrome coronavirus (MERS-CoV), which was reported in 2012². COVID-19 was of clustering onset and mainly affected the respiratory system with some patients rapidly progressing to acute respiratory distress syndrome (ARDS); other organ functions were less involved^3,4. Infection is transmitted through large droplets generated during coughing and sneezing by symptomatic patients but can also occur from asymptomatic people and before onset of symptoms⁵. Some patients had a low oxygenation index, indicating severe respiratory failure. Chest imaging findings suggested the involvement of both lungs. Chest computed tomography (CT) scans usually showed multifocal bilateral patchy shadows and/or ground-glass opacities; some patients showed a mixed pattern of ground-glass opacities and consolidation⁶. In a subset of patients, by the end of the first week, the disease can progress to pneumonia, respiratory failure, and death. This progression is associated with an extreme rise in inflammatory cytokines including IL2, IL7, IL10, GCSF, IP10, MCP1, MIP1A, and TNFα⁷. Corona viruses mainly recognize their corresponding receptors on target cells through S proteins on their surface; entry to the cells results in infection. A structure model analysis shows that SARS-CoV-2 binds to ACE2 with more than a 10-fold higher affinity than SARS-CoV, at a level above the threshold required for virus infection⁸. Specific diagnosis is by specific molecular tests on respiratory samples (throat swab/nasopharyngeal swab/sputum/endotracheal aspirates and bronchoalveolar lavage). The virus may also be detected in the stool and in severe cases, the blood⁹.

 

HISTORY AND ORIGIN OF SPREAD:

Coronaviruses were first discovered in the 1930s when an acute respiratory infection of domesticated chickens was shown to be caused by the infectious bronchitis virus (IBV)¹⁰. Arthur Schalk and M.C. In 1931 a new respiratory infection of chickens in North Dakota described by Hawn. Gasping and listlessness were used for characterizing infection of new-born chicks. The chicks' mortality rate was 40–90%¹¹. Fred Beaudette and Charles Hudson six years later successfully isolated and cultivated the infectious bronchitis virus which caused the disease¹². In the 1940s, two more animal coronaviruses, mouse hepatitis virus (MHV) and transmissible gastroenteritis virus (TGEV), were isolated¹³. It was not realized at the time that these three different viruses were related¹⁴.

 

Scientists found evidence of human coronaviruses evidence was found by a scientist in the late 1960s, particularly prevalent include 229E, NL63, OC43, and HKU1 Human coronavirus found in the noses of people with the common cold. The presence of the crown - like projections on their surfaces name “coronavirus”. in Latin “halo” or “crown” means “Corona”. During the winter months and early spring coronavirus infections in humans most often occur¹⁵. sense RNA viruseranging from 60nm to 140nm in diameter with spike-like projections on its surface are enveloped positive giving it a crown-like appearancehence the name coronavirus when observed under the electron microscope¹⁶.

In 2002– 2003 when a new coronavirus of the β genera and with origin in bats crossed over to humans via the intermediary host of palm civet cats in the Guangdong province of China¹⁷. Almost a decade later in 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV), also of bat origin, emerged in Saudi Arabia with dromedary camels as the intermediate host¹⁸. In later December 2019, a cluster of patients was admitted to hospitals with an initial diagnosis of pneumonia of an unknown etiology. These patients were epidemiologically linked to the seafood and wet animal wholesale market in Wuhan, Hubei Province, China^19,20. By January 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed COVID-19 infection, less than half of these patients had underlying diseases, including diabetes, hypertension, and cardiovascular disease²¹. These patients were presumed to be infected in that hospital, likely due to nosocomial infection.

 

STRUCTURE OF COVID-19:

Coronaviruses is large, roughly spherical, enveloped, positive-stranded RNA viruses with surface projections²² reference to the Fig. 1: Structure of COVID

 

. The average diameter of the virus particles is around 125 nm.They have the largest genome among all RNA viruses, ranging from 27 to 32 kb²³. The viral envelope consists of a lipid bilayer, in which the three structural proteins are present, The membrane protein (M) and the envelope protein (E) are involved in virus assembly, whereas the spike protein (S) mediates virus entry into host cells²⁴. The ratio of E:S:M is approximately 1:20:300²⁵. The spike forms large projected from the virus surface, giving coronaviruses the appearance of crownshence their name; corona. (In Latin means crown)²⁶. The coronavirus spike contains three segments which are as follows- a large ectodomain, a single-pass trans- membrane anchor and a short intracellular tail. The ectodomain consists of a receptor-binding subunit S1 and subunit S2. Electron microscopy studies revealed that the spike is a clove-shaped homotrimer with three S1 heads and atrimeric S2 stalk²⁷. During virus entry, S1 binds to a receptor on the host cell surface for viral attachment, and S2 fuses the host, allowing viral genomes to enter host cells. The E and M protein are important in forming the viral envelope and maintaining its structural shape .Receptor binding and membrane fusion are the initial and crucial steps in the coronavirus infection cycle; they also serve as primary targets for human inventions^28,29.

 

Fig. 1: Structure of COVID

 

GENETICS AND VIROLOGY:

Coronaviruses belong to the family Coronaviridae. They can be classified into four genera i.e. Alphacoronavirus, Beta coronavirus, Gamma coronavirus, and Delta coronavirus³⁰. Different genera’s can be further divided into subtypes which have been listed in

Table 1. The various genus of coronaviruses such as the Alphacoronavirus having the species Human coronavirus NL63, Human corona virus 229E, miniopterus bat coronavirus-1³¹ and Beta coronavirus consisting of species Bovine coronavirus, Human coronavirus OC43, Middle East Respiratory Syndrome-related corona virus (MERS), Severe acute respiratory syndrome related coronavirus(SARS-CoV, SARS-CoV-2)³². The Gamma coronavirus having the species of Avian corona virus, Beluga whale coronavirusSW1³³, and the Delta coronavirus consist of Bulbul coronavirus HKU11, Porcine coronavirus HKU15³⁴.

 

Table 1: Different strains of coronaviruses

Genus	Species
Alphacoronavirus	Human coronavirus NL63, Human corona virus 229E, miniopterus bat coronavirus 1.
Beta coronavirus	Bovine coronavirus, Human coronavirus OC43, Middle East Respiratory Syndrome related corona virus (MERS), Severe acute respiratory syndrome related coronavirus (SARS-CoV, SARS-CoV-2).
Gamma coronavirus	Avian corona virus, Beluga whale coronavirus SW1.
Delta coronavirus	Bulbul coronavirus HKU11, Porcine coronavirus HKU15.

 

The genome of COVID is a single-stranded positive-sense RNA with 5′-cap structure and 3′poly-A tail³⁵ the 5’ terminalencodes the replicateswhich is the nonstructural proteins responsible for viral replication within the cell^36,37. CoV genomes encode total 16 nonstructural proteins and they exhibit multiple functions required for viral replication³⁸ CoVs have the general genome organization: 5’UTR-polymerase gene and UTR 3’ - structural protein genes, where the UTR are untranslated regions. The structural protein genes of coronaviruses are in the order (HE)-S-E-M-N³⁹. Critical proteins for viral replication include the main protease (nsp5), the papain-like protease (nsp3), and the RNA-dependent RNA polymerase (nsp12, RdRp)⁴⁰. The other constituent proteins facilitate viral replication and disturb the intrinsic host immune functions⁴¹. The structure of the receptor-binding gene region is very similar to that of the SARS coronavirus and the virus use the angiotensin-converting enzyme 2 (ACE2) receptor for cell entry⁴².

 

PATHOPHYSIOLOGY:

Human-to-human transmission primarily occurs due to close contact and through respiratory droplets; large droplets of virus-laden mucus are the primary mode of transmission. Virus life cycle consists of a series of steps that begin with the viral binding with target cell and continue up to the viral replication⁴³. Once viral particles enter the respiratory tract, the virus attaches to pulmonary cells. SARS-CoV-2 (COVID-19) binds to ACE2 (the angiotensin-converting enzyme 2) receptor by its Spike protein and allows COVID-19 to enter⁴⁴. After the binding virus is internalized via endocytosis without access to the host intracellular compartment until a membrane fusion event occurs^45,42. This process is mediated by membrane-bound protease known as transmembrane serine protease 2 (TMPRSS2), which cleaves the S protein which is a necessary step for membrane fusion⁴⁶. Upon membrane fusion, viral RNA enters cytoplasmic membranes where the replication and transcription take place. RNA synthesis is mediated by the viral replicate, a huge protein complex⁴⁷. Once the virus enters the host cell, the viral RNA is exposed. Open reading frames 1a and 1ab (ORF1a and ORF1ab) are translated, producing polyproteins (pp1a and pp1ab)³⁷. These polyproteins are later cleaved to form structural proteins for the RNA replicase- transcriptase complex, which is responsible for the replication and transcription of viral RNA⁴⁸. Viral nucleocapsids are assembled and bud from the lumen of the endoplasmic reticulum Golgi intermediate compartment (ERGIC). As viral nucleocapsids enclosed viral RNA to produce new coronavirus virions, they are exocytosed which leads to the completion of the replication cycle⁴⁹. These viral lifecycle steps in Fig. 2 provide potential targets for drug therapy.

 

Immune Response:

In milder cases of SARS, a robust type I interferon response leads to appropriate adaptive immune responses which results in a viral clearance⁵⁰. In severe cases (SARS and MERS) decreased viral control is associated with a delayed or absent type I interferon response; instead, the initial response recruits neutrophils, monocytes, and macrophages to the lung, which is associated with increased immunopathology Fig. 2. The influx of myeloid cells into the lungsleads to cytokine storm, with increases in levels of serum pro-inflammatory cytokines ( IL-1, IL-6, IL-12, and TNFɑ ) that increase vascular permeability and decrease lung function⁵¹.

 

Fig. 2: Virus replication cycle and immune response

 

SYMPTOMS:

Based on the current epidemiological surveys, the incubation period of COVID is 1–14 days. The time after exposure and before having symptoms is called an incubation period. Cough cold, fever iscommon symptoms. Most of the people observed with mild symptoms

⁵². The virus can also lead to severe complications such as pneumonia, septic shock, cytokine Strome. Many of cases found with no symptoms⁵³.

 

Fig. 3: Symptoms of COVID-19

 

RECEPTOR RECOGNITION PATTERN OF CORONA VIRUSES:

Coronaviruses are a large family of single-stranded enveloped RNA viruses and can be divided into four major genera⁵⁴. Viral envelope glycoprotein initiate entry of viruses into cells by binding to cell surface receptors followed by conformational changes leading to membrane fusion and delivery of the genome to the cytoplasm⁵⁵. Prototypic α-genus coronaviruses mainly includeporcine transmissible gastroenteritis coronavirus (TGEV), human coronavirus NL63 (HCoV-NL63), and porcine respiratory coronavirus (PRCV). Prototypic β-genus coronaviruses include mainly Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and bovine coronavirus (BCoV)mouse hepatitis coronavirus (MHV). Prototypic γ-genus coronaviruses include avian infectious bronchitis virus (IBV)^56–58 reference to the Fig. 4. Numerous lines of research studies have been carried out that which host is susceptible to SARS-CoV infection which is primarily determined by the affinity between the viral RBD and host ACE2 in the initial viral attachment step^59–61. S1 domains and their complexes with their respective receptor have elucidated many puzzles which analyses of crystal structures of coronavirus mainly associated with coronavirus-receptor interactions. Since the crystal structures of five coronavirus S1 domains complexed with their respective receptor have been determined. These are the β-genus SARS-CoV S1-CTD complexed with human ACE2⁶².

 

Fig. 4: Receptor binding of different genomes of Coronavirus

 

CASE STUDY:

Brazil's total number of cases has grown five fold in less than a month, from 85,000 on May 1 to 438,000 on May 29Error! Reference source not found.. There have also been significant rises in other Latin American countries like Peru, Chile, and Mexico. The United States has now experienced more than 100,000 fatalities, according to statistics from Johns Hopkins University. While its pace of increase has dropped overall, some areas that have reopened their economies have seen a rising number of infections, and the battle with the coronavirus is far from over in the country. Worldwide, there are now 5.7 million cases and more than 350,000 fatalities as shown in

Table 2⁶³

 

Table 2: Worldwide data of corona Active patients and Fatalities are listed

Countries	Active	Fatalities
United States	1,699,073	100,396
Brazil	411,821	25,598
Russia	370,171	3,962
Britain	267,240	37,460
Spain	236,769	27,118
Italy	231,139	33,072
Germany	181,524	8,428
Turkey	159,797	4,431
India	151,767	4,337
France	145,746	28,595
Iran	141,591	7,564
Peru	135,905	3,983
Canada	87,508	6,765
China	82,993	4,634
Chile	82,298	841
Saudi Arabia	78,541	425
Mexico	74,560	8,134
Pakistan	59,151	1,225
Japan	16,683	867
SouthKorea	11,344	269

 

DIAGNOSIS:

The U.S. CDC has developed criteria for persons under investigation (PUI)⁶⁴. If a person is deemed a PUI, immediate prevention and infection control measures are undertaken. Epidemiological factors are used to assess the requirement of testing. These include close contact with a laboratory-confirmed patient within 14 days of symptoms or travel history⁶⁴. For patients who meet diagnostic criteria for SARS-CoV-2 testing, the CDC recommends a collection of specimens from the upper respiratory tract (nasopharyngeal and oropharyngeal swab) and,if possible, the lower respiratory tract (sputum, tracheal pirate,or bronchoalveolar lavage)⁶⁵. Performing real-time fluorescence (RT-PCR) to detect the positive nucleic acid of SARS-CoV-2 in sputum, throat swabs, and secretions of the lower respiratory tract samples are the following procedures have been suggested for diagnosis of suspected patients^66–68. If a positive test result is achieved, it is recommended to repeat the test for verification purposes. A negative test with a strong clinical suspicion also warrants repeat testing⁶⁴.

 

Laboratory Findings:

Among COVID-19 patients, common laboratory abnormalities include lymphopenia^69–71 prolonged prothrombin time, and elevated lactate dehydrogenase⁷¹. Patients in the intensive care unit have shown higher levels of interleukin (IL) 2, IL-7, IL-10, GCSF (granulocyte colony-stimulating factor), IP10 (interferon gamma-induced protein 10), MCP1 (monocyte chemotactic protein 1), MIP1A (macrophage inflammatory protein alpha), and TNF-α (tumor necrosis factor-α)⁷².

 

Radiology Finding:

In a study describing 41 of the initial cases of 2019-nCoV infection, all 41 patients had pneumonia with abnormal findings on the chest computed tomography (CT-scan)⁷². Abnormalities on chest CT-scan were also seen in another study of 6 cases in which all of them showed multifocal patchy ground-glass opacities notably nearby the peripheral sections of the lungs⁷³. As the disease course continues, mild to the moderate progression of disease was noted in some cases which manifested by extension and increasing density of lung opacities⁷⁴. Bilateral multiple lobular and sub segmental areas of consolidation are typical findings on the chest CT-scan of ICU-admitted patients⁷².

 

TREATMENT:

The person-to-person transmission of COVID-19 infection led to the isolation of patients. At present, there are no specific antiviral drugs or vaccines against COVID- 19 infections for potential therapy of humans. The only option available is using broad-spectrum antiviral drugs like Nucleoside analogs and also HIV-protease inhibitors that could attenuate virus infection until the specific antiviral becomes available⁷⁵. Chloroquine and hydroxychloroquine appear to block viral entry into cells by inhibiting glycosylation of host receptors, proteolytic processing, and endosomal acidification^76,77. Favipiravir, previously known as T-705, is a prodrug of a purine nucleotide, favipiravir ribofuranosyl-5′-triphosphate. The active agent inhibits the RNA polymerase, halting viral replication⁷⁸. The first clinical use of remdesivir was for the treatment of Ebola⁷⁹; however, successful case reports describing the use of remdesivir for COVID-19 have been reported in the

Table 3:A summaries of the drugs selected for treatment

Agent	Target	Contraindications	Toxicities	Drug-drug interaction
Chloroquine phosphate	Blockade of viral entry by inhibiting glycosylation of host receptor, proteolytic processing.	Hypersensitivity to chloroquine,4-aminoquinoline compounds	Abdominal cramps, anorexia, nausea, vomiting retinal toxicity, central nervous system effects	CYP2D6 and CYP3A4
Hydroxy chloroquine sulfate	Same mechanism as of chloroquine	Hypersensitivity to hydroxychloroquine,4-aminoquinoline, and other formulation compounds	Same as chloroquine but less common	CYP2D6 and CYP3A4, CYP3AS
Remdesivir	RNA polymerase inhibitor	Exclusion criteria based on a protocol	Elevated transaminases, kidney injury	Not a significant inducer/inhibiter of CYP enzymes
Tocilizumab	IL-6 inhibition reduction in a cytokine storm	Known hypersensitivity with tocilizumab and caution with neutropenia patients	Increase in upper respiratory tract infections and hypertension	IL-6 reduces mRNA expressions for CYP450 and CYP3A4 isoenzymes
Favipiravir	RNA polymerase inhibitor	Exclusion criteria based on a protocol	Elevated transaminases and reduction in neutrophil count	CYP2C8 and aldehyde oxidase inhibitor

 

^80,81.

 

Isolation and supportive care including oxygen therapy, fluid management, and antibiotics treatment for secondary bacterial infections are recommended⁸². Some COVID-19 patients progressed rapidly to ARDS and septic shock, which was eventually followed by multiple organ failure^69,72. Patients with mild infections require early supportive management. This can be achieved with the use of acetaminophen, external cooling, oxygen therapy, nutritional supplements, and anti-bacterial therapy⁸³. Critically ill patients require high flow oxygen, extracorporeal membrane oxygenation (ECMO), glucocorticoid therapy, and convalescent plasma⁸³. The administration of systemic corticosteroids is not recommended to treat ARDS⁶⁴. Furthermore, there are several other compounds are in development. EIDD-2801 compound that hasshown high therapeutic potential against seasonal and pandemic influenza virus infections and this represents another potential drug to beconsidered for the treatment of COVID-19 infection⁸⁴.

 

Therapies:

·       Monoclonal Antibodies:

Monoclonal antibodies directed against key inflammatory cytokinesor other aspects of the innateimmune response represent another potential class of adjunctive therapies for COVID19. The rationale for their use is that the underlying pathophysiology of significant or damage in the lungs and other organs is caused by an amplified immune response and cytokine release, or “cytokinestorm”⁸⁵. Thus, monoclonal antibodies against IL-6 could theoretically dampen this process and improve clinical outcomes⁸⁶. Inhibition fusion of CoV with human cells and to decrease the mortality rate in SARS-CoV-infected patients was shown by monoclonal antibodies (from convalescent human plasma, animal plasma, or manufactured) against the spike glycoprotein S^87–93. A protein, which also inhibits the spike glycoprotein S, although it is not a monoclonal antibody, has been isolated from a red alga called Griffithsia However to date, it has only been tested in animal studies⁹⁴. Tocilizumab, a monoclonal antibody IL-6 receptor antagonist, is FDA approved to treat RA and cytokine release syndrome following chimeric antigen receptor T-cell therapy shown in

Table 3:A summaries of the drugs selected for treatment

Agent	Target	Contraindications	Toxicities	Drug-drug interaction
Chloroquine phosphate	Blockade of viral entry by inhibiting glycosylation of host receptor, proteolytic processing.	Hypersensitivity to chloroquine,4-aminoquinoline compounds	Abdominal cramps, anorexia, nausea, vomiting retinal toxicity, central nervous system effects	CYP2D6 and CYP3A4
Hydroxy chloroquine sulfate	Same mechanism as of chloroquine	Hypersensitivity to hydroxychloroquine,4-aminoquinoline, and other formulation compounds	Same as chloroquine but less common	CYP2D6 and CYP3A4, CYP3AS
Remdesivir	RNA polymerase inhibitor	Exclusion criteria based on a protocol	Elevated transaminases, kidney injury	Not a significant inducer/inhibiter of CYP enzymes
Tocilizumab	IL-6 inhibition reduction in a cytokine storm	Known hypersensitivity with tocilizumab and caution with neutropenia patients	Increase in upper respiratory tract infections and hypertension	IL-6 reduces mRNA expressions for CYP450 and CYP3A4 isoenzymes
Favipiravir	RNA polymerase inhibitor	Exclusion criteria based on a protocol	Elevated transaminases and reduction in neutrophil count	CYP2C8 and aldehyde oxidase inhibitor

 

⁸⁶.

·       Cellular Therapy:

COVID-19 is known to be associated with overt inflammatory responses^69,72. The useof mesenchymal stromal cells obtained from allogeneic donors in cellular therapy facilitates the regeneration of damaged cells and thus is effective in reducing non-productive inflammation inpatients⁹⁵. Studies have shown that autologous hematopoietic stem-cell transplant could result inshort-term expansion and isolation of antivirus-directed T cells for cytomegalovirus infection treatment.Hence, the expansion of anti-SARS-CoV-2-specific T cells is believed to be potential adjunct treatment for patients diagnosed with COVID-19⁹⁶.

 

·       Herbs For COVID-19

In the case ofCoronavirus, the viral entry is mediated by the Receptor-Binding Domain (RBD) of its spike (S)glycoprotein, which binds to the host cell receptor Angiotensin-Converting Enzyme-2 (ACE2)^97,98. RBD has been an attractive target for the researchers to abrogatecoronavirus infection and suggested that certain human antibodies recognized RBD on the S1domain and inhibited the viral infection by blocking the attachment of ACE2^99,100. Withania somnifera (L.) Dunal (Solanaceae), commonly known as Ashwagandha, one of the mostvalued medicinal plants of the traditional Indian systems of medicines, is used in more than 100formulations ofAyurveda, and is thought to be therapeutically equivalent to Ginseng¹⁰¹

 

Table 3:A summaries of the drugs selected for treatment

Agent	Target	Contraindications	Toxicities	Drug-drug interaction
Chloroquine phosphate	Blockade of viral entry by inhibiting glycosylation of host receptor, proteolytic processing.	Hypersensitivity to chloroquine,4-aminoquinoline compounds	Abdominal cramps, anorexia, nausea, vomiting retinal toxicity, central nervous system effects	CYP2D6 and CYP3A4
Hydroxy chloroquine sulfate	Same mechanism as of chloroquine	Hypersensitivity to hydroxychloroquine,4-aminoquinoline, and other formulation compounds	Same as chloroquine but less common	CYP2D6 and CYP3A4, CYP3AS
Remdesivir	RNA polymerase inhibitor	Exclusion criteria based on a protocol	Elevated transaminases, kidney injury	Not a significant inducer/inhibiter of CYP enzymes
Tocilizumab	IL-6 inhibition reduction in a cytokine storm	Known hypersensitivity with tocilizumab and caution with neutropenia patients	Increase in upper respiratory tract infections and hypertension	IL-6 reduces mRNA expressions for CYP450 and CYP3A4 isoenzymes
Favipiravir	RNA polymerase inhibitor	Exclusion criteria based on a protocol	Elevated transaminases and reduction in neutrophil count	CYP2C8 and aldehyde oxidase inhibitor

 

Withanolides present in roots and leaves of W. Somnifera were docked against ACE2-RBD complex. The phytocompound which bound to the interface was subjected to targeted/focused docking. At the ACE2-RBD complex, the phytocompounds were bound tightly. At the interface of the receptor and RBD, only the Withanone bound. Therefore, Withanone was analyzed further to study its role in blocking or weakening the interactions between the ACE2 receptor and RBD¹⁰².

 

SAFETY MEASURES:

·       Wash your hands regularly and perform hand hygiene with soap and water for at least 20 seconds. 60% alcohol based Sanitizers should be used.

·       Maintain social distancing and avoid crowded places.

·       Touching your face, nose, eyes and, the mouth should be avoided.

·       Implement respiratory hygiene.

·       Seek medical care if you have fever, cough and breathing problems.

·       Healthcare provider has given the advice to be followed.

·       Use sanitizer whenever needed.

·       Regularly checking their temperature, andinformimmediately to their doctor if they having symptoms such as shortness of breath, cough, or fever¹⁰³.

·       Moreover, women who have a travel history or COVID-19 symptoms should be kept in isolation for at least 14 days.

·       Face masks should be provided to patients who are coughing.

·       The National Health Commission of China proposed that neonates from mothers who are confirmed or suspected cases should be kept under observation and not breastfed.

·       Patients with respiratory symptoms should be asked to usesurgical masks

·       Personal protection equipment (PPE) is mandatory while treating such patients¹⁰⁴.

 

FUTURE PERSPECTIVE:

Extensive measures to reduce person-to-person transmission of COVID-19 are required to control the current outbreak. Special attention and efforts to protect or reduce transmission should be applied to susceptible populations including children, health care providers, and elderly people. A guideline was published for the medical staff, healthcare providers, and, public health individuals and researchers, and who are interested in the 2019-nCoV¹⁰⁵.

 

The public services and facilities should provide decontaminating reagents for cleaning hands on a routine basis. Physical contact with wet and contaminated objects should be considered in dealing with the virus, especially agents such as fecal and urine samples that can potentially serve as an alternative route of transmission^106,107.

 

An unprecedented disaster, especially in the most afflicted countries including China, Italy, Iran, and the USA the COVID-19 outbreak is proving to be in all aspects, especially health, social, and economic. It is too early to forecast any realistic scenario, but it will have a strong impact on World Wide¹⁰⁸. In addition to this hopeful low impact, if the prevention measures will be implemented, we could register a lower incidence of hygiene-linked diseases that still represent the leading causes of death¹⁰⁹. A vaccine is under development.

 

CONCLUSION:

The 2019 novel coronavirus (2019-nCoV) or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as it is rapidly spreading to the rest of the world from its origin in Wuhan City of Hubei Province of China. Now it is spread to each, and every corner of the world has numerous patients who are treated technically with a variety of treatment measures followed by the different countries. The resembling structure and different strains are reviewed in the following data with structure and receptor binding mechanisms are shown. The public services and facilities should provide decontaminating reagents for cleaning hands on a routine basis. Physical contact with wet and contaminated objects should be considered indealing with the virus, especially agents such as fecal and urine samples that can potentially serve as an alternative route of transmission. Wearing masks and washing hands with soaps and sanitizers. Therapies such as monoclonal antibodies, antiviral and herbal drugs are used for a recent treatment basis. In addition to this hopeful low impact, if the prevention measures will be implemented, we could register a lower incidence of hygiene-linked diseases that still represent the leading causes of death.

 

DECLARATION OF INTEREST:

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

 

ACKNOWLEDGEMENTS:

The authors acknowledge this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

 

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