A coadunation of biological and mathematical perspectives on the pandemic COVID-19: A Review

Coronaviruse disease (COVID-19) outbreak has created an emergency globally, and social distancing and isolation is the only solution to prevent its spread. Several countries have announced fully locked on to tackle this pandemic. The recent COVID-2019 has shaken the globe with incidence cases of more than halfmillion cases, and a mortality toll of more than twenty thousand to date. The coronavirus family is inclusive of pathogen of both – animal species and humans, encapsulating the isolated severe acute respiratory syndrome coronavirus (SARS-CoV). Researchers round the globe have been dexterously working to decode this lethal virus. Many mathematical frameworks have also been depicted which have helped to understand the dynamics of the COVID-19. Research on coronaviruses continues to explore various aspects of viral replication and pathogenesis to understanding the predilection of these viruses to switch between species, to develop an infection in a new host, and to identify significant reservoirs of coronaviruses will dramatically aid in our potential to prophesize when and where potential epidemics may occur. Many of the non-structural and accessory proteins encoded by the viruses remain unclear and unknown. This systematic review highlights the current situation of the pandemic, virus genomic composition, pathogenesis, symptomatology, diagnosis, and prognosis along with mathematical models of disease transmission and dynamics.


Introduction
A novel coronavirus (nCoV), named as ''2019-nCoV'', is causing the deadliest pandemic in late 2019 and early 2020, defined as the coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO). It is also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is the janitor for the recent sequential spread which began in Wuhan, China, early December 2019 (Huang et al., 2020;Zhou et al., 2020;Zhu et al., 2020. This outburst has been affiliated with the humongous scale of seafood and animal market in Wuhan, which has been the potential site of the spread of the virus infection. According to the Chinese Center for Disease Control and Prevention reports (China-CDC, 2020), the number of infected people has grown from hundreds to thousands not only in China but around the globe. During February-March, 2020, the apex spread of this viral disease has latched itself to people and is growing rapidly in Europe, North America, Asia, and the Middle East, while the first confirmed cases identified in African and Latin American countries. The number of cases of COVID-19 has drastically grown up since 16 th March, 2020 outside China. It is said that the carriers and reservoirs of this virus are bats and snakes (Leung, 2020;Zhou et al., 2020). Fig. 1 depicts the transmission of nCov-19 from Wuhan, China to the globe. the Torovirinae families respectively (Fehr & Perlman, 2015). The coronavirus family is inclusive of pathogens of both -animal species and humans, encapsulating the isolated severe acute respiratory syndrome coronavirus (SARS-CoV). Human coronaviruses were first described in the 1960s and are said to have the onus for severe respiratory tract infections (Fehr & Perlman, 2015). The coronaviruses are the janitors, leading to serious respiratory and gastrointestinal tract infections. They further have bifurcations in genera namely-new cases versus recoveries, death rate versus recovery rate and distribution of cases in China and outside China during the period January 22 to March 25, 2020. There has been a huge exponential jump after 10 th March, 2020 in COVID-19 cases in outside China (Fig. 2). These cases may grow even further shortly as per CDC estimation.

Genomic Composition
It has been observed that RNA viruses often carry out selective packaging of their genomes in a myriad of ways involving a genomic packaging signal. The first coronavirus packaging signal was studied thirty years back  howbeit; its preliminary functioning is still unknown. As previously mentioned, coronaviruses are composed of a non-segmented, positive-sense RNA genome of about ∼30 kb, which is inclusive of a 5' cap entity in combination with a 3' poly (A) tail which aids act as an mRNA for the translation of the replicase polyproteins (Fehr & Perlman, 2015). The replicase gene forming the non-structural proteins (NSP) occupies the majority (~20kb) of the genome when compared to the structural and accessory proteins which occupy the remaining 10kb. The 5' end of the genome includes -a preliminary sequence and an untranslated region (UTR) containing multiple stem-loop structures necessary for RNA replication and transcription purpose. Moreover, many transcriptional regulatory sequences (TRSs) are attached at the initiation point of every structural gene important for their expression. The 3' UTR is also composed of RNA structures mandatory for replication and production of the viral RNA. The symmetrical arrangement of the coronavirus genome is 5'-preliminary-UTR-replicase-S (Spike)-E (Envelope)-M (Membrane)-N (Nucleocapsid)-3'UTR-poly (A) tail in combination with accessory genes randomly dispersed within the structural genes at the 3' end of the viral genome (Fig. 3). The accessory proteins may play an important role in viral pathogenesis even though not in replication (Fehr & Perlman, 2015).
There are three important parameters for coronavirus genome packaging -a) viral infection includes not only replication of gRNA but also the formation of subgenomic (sg) RNAs which act as mRNAs for genes present downstream, b) coronaviruses have helically symmetric icosahedral nucleocapsids (Masters, 2006;Neuman et al., 2006;Gui et al., 2017) which is simply not common for a positive-strand RNA virus and c) the arrangement of the nucleocapsid into the virion initiates via interactions between the -C terminal of multiple monomers of N and M proteins (Escors et al., 2001& Masters, 2019. The packaging of coronavirus is quite a challenge to obtain a specific recognition and selection of gRNAs and other RNA species (Masters, 2019).

The viral envelope
It is the outermost part of a virus, provides strength, rigidity and a definite shape. It comprises of Spike (S), Envelope (E) and Membrane (M). The subgroup of coronaviruses like Betacoronaviruses subgroup A has spike like protein structures embedded in the membrane called Hemagglutinin esterase (HE). SARS-CoV-2 differs from other viruses because it expresses HE (Schoeman & Fielding, 2019).

Glycosylated spike (S):
For an easy entry inside the host cell, a densely glycosylated spike is used by the virus. S protein is a trimeric class I fusion protein that exists in a metastable prefusion conformation that undergoes a substantial structural rearrangement to fuse the viral membrane with the host cell membrane. The 3D structure of spike demonstrates that there exists a single Receptor Binding Domain (RBD) in the up conformation. As the RBD undergoes a hinge-like movement, S1 subunit becomes visible along with S2 unit (more stable). The S1 subunit determines the virus-host range and cellular tropism by RBD. The S2 mediates virus-cell membrane fusion by HR1 and HR2. This stochastic RBD movement is found in closely related beta-coronaviruses SARS-CoV and MERS-CoV and distantly related alpha-coronaviruses (PEDV). This mechanism in 2019-CoV indicates a similar trigger system in Coronaviridae, where receptor (ACE2) that binds to the RBDs forms 3 RBD up conformations (unstable) that results in the shredding of S1 and S2 refolding. Fig. 5 demonstrates the RBD of spike complexed with the ACE2 receptor (Protein Data Bank). The overall spike structure of 2019-nCoV resembles to that of SARS-CoV spike. The minor difference between the two is the position of RBD in their respective down conformations.
The spike of SARS-CoV-2 has a higher affinity for ACE2 receptor on the host, approximately 10 times more than the SARS-CoV affinity (Hoffmann et al, 2020 Small molecules like NAG (N-acetyl-D-glucosamine) are found on both the chains whereas Zn ion is found only on the ACE2 receptor.

Envelope protein (E):
Short integral membrane protein of 76-109 amino acids, from 8.4 to 12 kDa in size. Envelope has a short, hydrophilic amino terminus consisting of 7-12 amino acids, and then a large hydrophobic TMD of 25 amino acids and ends with a long, hydrophilic carboxyl terminus. The hydrophobic region of TMD has amphipathic alpha-helix that oligomerizes to form an ion-conductive pore in membranes. The TMD has 2 nonpolar, neutral amino acids valine and leucine, lending a strong hydrophobicity to the E protein, with an overall net charge zero. The middle region is uncharged and flanks on one side by N terminus and another side by C terminus (exhibits some hydrophobicity) of variable charge.
The E protein has a bonding motif known as postsynaptic density protein 95 (PSD95) (PDZ)binding-motif (PBM). The PDZ domain is a protein-protein interaction module that can bind to the C-terminus for target proteins such as cellular adapter proteins involved in host-cell processes important for viral infection (Schoeman & Fielding, 2019). The PBM region can either be deleted or mutated but it reverts to a pathogenic state. PBM mutations appear to be tolerated but that a reasonably intact PBM domain is still necessary to avoid revertant mutants. E protein interacts with M to form the viral envelope (Schoeman & Fielding, 2019).

Membrane protein (M):
The integral membrane protein M is a region of membrane for virus assembly, responsible for the transmembrane transport of nutrients, bud release and envelope formation and its shape determination. Two functionally distinct forms of coronavirus M protein are there. Both types of M visible on viral particles are larger than assumed for a single M protein. The formation of a convex, rigidified viral envelope is dependent on the presence of one form of M, which is called MLONG. Statistical evidence indicates that spike incorporation is linked to particle size and that spikes cluster in regions where MLONG is generally present (Neuman & Kiss, 2011).

Hemagglutinin Esterase (HE):
The hemagglutinin esterases (HEs) a homodimeric class I membrane protein are a family of viral envelope glycoproteins that causes reversible attachment to O-acetylated sialic acids by acting both as lectins and as receptor-destroying enzymes (RDEs). Enzymatic activity is associated with the hemagglutinin-esterase (HE), CoV HEs lack membrane fusion activity and, in the virion, they are accessory to the spike protein S (Zeng et al., 2008).

The nucleocapsid
It is protected by the viral envelope by strong surroundings. The positive-sense single-

The Life Cycle of Coronavirus
SARS-CoV-2 begins its life cycle when its glycosylated S protein binds to the cellular receptor ACE2 just like SARS-CoV. Fig. 6 shows how the interaction for entry occurs (Jiang et al., 2012). After receptor binding takes place with the help of TMPRSS2 (splits S protein for further penetration) S protein priming and conformational change in the S protein occurs that facilitates viral envelope fusion with the cell membrane of the target cell through the endosomal pathway (Hoffmann et al., 2020). However, camostat mesylate, an inhibitor of TMPRSS2 can block lung infection. The antibody response against SARS-CoV is efficient therefore it can be expected that similar kind of antibody neutralization might occur in the SARS-CoV-2 infection to some degree.SARS-CoV-2 then releases its genetic material i.e., +ssRNA into the host cell. Genome RNA composition is (5'UTR-Gene orf1ab--Gene S- Genome RNA is translated into viral replicase polyproteins pp1a and 1ab, which are then cleaved into small products by viral proteinases. Fig. 7 depicts the life cycle of the virus inside a host.

Animal Coronaviruses
Coronaviruses are responsible for causing myriad diseases in animals such as -pigs, chickens, dogs, cats, and cows which led to gargantuan research in the previous decade. Feline enteric coronavirus (FCoV) causes a mild or asymptomatic infection in domestic cats, but during persistent infection, mutation transforms the virus into a highly virulent strain of FCoV (Feline Infectious Peritonitis Virus, FIPV) progresses to the formation of a mortal disease namely -feline infectious peritonitis (FIP), which is of both the forms -wet and dry, quite similar to the sarcoidosis, which is a human disease. This virus is said to be lethal as it disturbs the cytokine and the chemokine expression leading to lymphocyte depletion (Perlman & Netland, 2009). Howbeit, this hypothesis is still not confirmed yet. On the other hand, bovine CoV, rat CoV, and infectious bronchitis virus (IBV) lead to benign to acute respiratory tract infections in cows, rats, and chickens respectively. Bovine CoV has been held responsible for an apex loss in the cattle industry as it infects cattle and spreads to other animals such -camel, deer, and elk, causing winter dysentery (diarrhoea), dehydration, weight loss, animal depression, lackadaisical attitude and also reduced milk production. IBV strains, namely -γ-coronavirus, are the janitors that affect the urogenital tract of chickens causing kidney disorders. Moreover, it reduces egg production in chicken and abnormal weight gain in chickens which is a significant loss in the poultry industry annually (Perlman & Nestland, 2009 (Levy et al, 2000).

Human Coronaviruses
Before SARS-CoV epidemic, coronaviruses were considered to be not-so-serious respiratory infections in humans. It is being reiterated again, two major coronaviruses in humans are -Alpha-coronaviruses (HCoV-229E and HCoV-NL63) and are Beta-coronaviruses (HCoV-OC43 and HCoV-HKU1). HCoV-229E and HCoV-OC43 were retrieved 50 years ago (McIntosh et al, 1967;Bradburne et al, 1967;Hamre & Procknow, 1966). HCoV-NL63 and HCoV-HKU1 have been determined during the previous SARS-CoV outbreak (Woo et al, 2005& van der Hoek et al, 2004. These viruses lead to respiratory tract infections in 15-30% of the human populace and have been observed to be very serious in the elderly population as well as in individuals who endure cancer or any other immunological disorder (Fehr & Perlamn, 2015). HCoV-NL63 has the onus of causing laryngotracheitis (van der Hoek et al, 2005). One interesting aspect of these viruses is variance in their genetic variability (Fehr & Perlman, 2015).
A group 2b β-coronavirus namely -SARS-CoV was first determined which was responsible for Severe Acute Respiratory Syndrome (SARS) spread in China during the year 2002-2003.
During this outburst, around 8098 cases were observed with 774 lethalities leading to the death rate of 9%. Elderly people were morbid and mortality was also high in this section of individuals. This virus often attacks the epithelial cells within the lung and has the potential to penetrate the macrophages and dendritic cells (Peiris et al, 2003& Spiegel et al, 2006.
The novel coronavirus which has now become a pandemic around the globe is also said to belong from the beta-BAT-SARS-coronavirus family .
Another novel human CoV emerged in the Middle East back in 2012 whose nomenclature is -Middle East Respiratory Syndrome-CoV (MERS-CoV). It was observed to lead sequential pathogenic respiratory infections in Saudi Arabia and other countries in the Middle East (Zaki et al, 2012). With its rapid spread, it was assumed that it would lead to an apex and a very serious outburst, however, in 2013 newer cases never showed up. In 2014, an unpredictable outshoot of almost 200 cases and 40 mortalities from human-to-human transmission. Fig. 8 below represents the various levels of transmission and pathogenesis of the coronavirus. The level 0 represents the inactive coronavirus itself, which then enters an animal host, which is level I. Level II is a broader domain which is the transmission of the virus from animal-to-human and human-to-human respectively.

Signs and symptoms of COVID-19
The most convincing mode of this virus transmission is said to be inhalation of contaminated/infectious aerosols whose incubation period is 3-14 days (CDC, 2020a). The disease caused by COVID-19 may range from asymptomatic to fatal disease. Underlying health conditions that enhance the susceptibility are hypertension, chronic obstructive pulmonary disease, diabetes, cardiovascular disease (Guo et al., 2020). Severe complications that might arise due to getting infected are respiratory distress syndrome, septic shock, metabolic acidosis which is hard to correct, coagulation dysfunction and multiple organ failure. Cytopathic effect (CPE) and cytokine storm or sustained inflammatory responses, hypoxia, septic shock etc. may be related to the critical conditions of SARS-CoV-2 infected patients (https://www.mayoclinic.org/). Fig. 9 describes the symptoms of COVID-19. The severity of infection may vary from person to person and even from an age group to another age group. People already possessing chronic illnesses like Blood disorders (e.g., sickle cell disease or on blood thinners), chronic kidney, chronic liver disease (e.g., cirrhosis, chronic hepatitis), compromised immune system (immunosuppression) (chemotherapy or radiation, transplant, HIV or AIDS), current or recent pregnancy in the last two weeks, endocrine disorders (e.g., diabetes mellitus), metabolic disorders (such as inherited metabolic disorders and mitochondrial disorders), heart disease (such as congenital heart disease, congestive heart failure, and coronary artery disease), lung disease (chronic bronchitis or emphysema), neurological and neurologic and neurodevelopment conditions including disorders of the brain, spinal cord, peripheral nerve, and muscle such as cerebral palsy, epilepsy (seizure disorders), stroke, intellectual disability, moderate to severe developmental delay, muscular dystrophy, or spinal cord injury are more prone to getting serious infection and reestablishment of health might be difficult. People belonging to older age groups, lacking efficient immune responses are also in close proximity to hazardous effects (Guo et al., 2020).
Manifestations are progressive in some cases to severe symptoms that can eventually lead to death are:

Detection, Diagnosis & Prognosis
In order to diagnose COVID-19, like other viral diseases it composed of techniques that help to determine the presence of the virus and antibodies which develop in response to the infection. Because of limited screening, no countries had trustworthy data on the spread of the virus in their populace (Ioannidis, 2020).

Detection & Diagnosis Approaches
a) Imaging Investigations: A chest CT scan is one of the most prominent imaging investigations which is aiding medical consultants to screen for the disease, also helps understanding lung pathology. In a recent in 919 patients defined the typical early growth of COVID-19 as "bilateral multilobar ground-glass opacification (GGO) alongwith a posterior spread" (Salehi et al, 2020). Another pivotal study discerns that the CT imaging investigation proves to be better than the RT-PCR method for CVD-19 infection with a sensitivity of 98%, but, since this was performed in China, it cannot be generalized for all (Ai & Yang, 2020). In one of the recent studies, it was established that Chinese radiologists showcased about 72-94% sensitivity and 24-94% in distinguishing nCoV-19 from other viral infections using CT imaging (Bai et al, 2020).

b) rRT-Polymerase Chain Reaction for virus detection: Deploying real-time reverse
transcription-polymerase chain reaction (rRT-PCR) is the easiest way to figure out the infection in patients which can be done by taking the patients respiratory samples such asnasopharyngeal swab or sputum sample (CDC, 2020). These results are available within a frame of either a few hours from the test to 2 days. This molecular biochemistry examination helps to identify the genomic composition. The initial PCR tests were produced at Charité in

Prognosis
Since the outbreak of nCoV-19 worldwide, pharmacists and researchers are working towards determining the potential drugs which can be used as an efficient treatment for COVID-19.
The entire globe is desperate to find effective treatments for this treacherous viral disease.
Although, viral diseases have affected mankind in the past, howbeit, we still lack anti-viral therapeutics. Traditionally, interferons (IFNs) are only partially effective against coronaviruses (Cinatl et al, 2003). IFNs along with ribavirin have showcased to increase the efficacy when IFNs were employed individually against coronaviruses. The previous outbreaks of the SARS-CoV and MERS-CoV have allowed determining humongous number of potential anti-viral drug leads namely -viral proteases, polymerases, and entry proteins.
Unfortunately, much work yet remains in this domain of research. Approved vaccines are present for IBV, TGEV, and Canine CoV, however, they are not much effective in preventing the disease. As far as SARS-CoV is concerned, several potential vaccines such asrecombinant attenuated viruses, live virus vectors, or mono viral proteins expressed from DNA plasmids, are available but none of them are approved yet. Conventionally, it has been considered that live attenuated vaccines would be efficacious in targeting the coronaviruses.
Vaccine generation for coronaviruses is an apex challenge and has seen many ups-downs in the past (Saif et al, 2004).
Since March, 2020, many drug candidates have been subjected tor clinical trials for their development of vaccines and treatments. These drugs mainly include compounds that are used to treat flu, malaria, Ebola disease (Khan et al., 2017). Table 1 summarises the conventional drug leads which have been subjected to clinical trials for COVID-19.

Mathematical Models of COVID-19 Transmission and Dynamics (MFS)
COVID-19 has spread rapidly worldwide, and WHO and CDC have labeled it as a "pandemic".
Therefore, it becomes necessary to develop and use the mathematical approach to study the pathogenesis of SARS-CoV-2 in humans. There are a few literature available that are inclined towards the mathematical modeling for this virus Huang et al, 2020;Chan et al, 2020;Zhu et al, 2020;Bogosh et al, 2020;Wu et al, 2020c). The motive of these researches was to calculate the basic reproduction number ( ) by using Ordinary differential equations (ODEs), Markov Chain Monto Carlo methods (MCMC) (Wu et al, 2020c) or using intrinsic growth rate and serial intervals Zhao et al, 2020a;Zhao et al, 2020b). In this section, we discuss five major models that exists in literatures that can help us understand the transmissibility of the SARS-CoV-2 from its natural reservoirs to humans. Chen et al. (2020) developed a mathematical model for simulating the phase-based transmissibility of the SARS-CoV-2. They used the data from the published literatures (Longini et al., 2005;Zhou et al, 2020;WHO, 2020(a); Japan MoH, 2020; WHO, 2020(b); WHO, 2020(c)). The assumption was that the virus first spreads among the bats and then is transmitted to some wild animals which were hunted and lastly delivered to the seafood market. These were now the 'reservoir of the viruses'. People visited the market and therein got infected. The model is based on the following parameters:
2) The SARS-CoV-2 in a reservoir (the seafood market) was taken as . The retail purchase rate of the hosts in the market was assumed as . The transmission rate of infection through symptomatic infected people and asymptomatic infected people into was denoted by and 3) , and denoted the birth rate of bats, hosts, and people, respectively, whereas and were taken as the death rate of the latter. The birth and the death rate of people during the outbreak were quite less. However, people who traveled, either migration or immigration across the Wuhan city reason being a bar, thus, and was taken as the rate of people coming into the city of Wuhan and going out of the city of Wuhan accordingly. and was taken as the total number of bats, hosts, and people, respectively.

4)
, and denoted the new born bat, new born host and new born people, respectively and defined by , and 5) The incubation period of the bat infection, host infection and human infection was denoted by 1/ , t and t respectively, and the infectious period of bat infection, host infection and human infection was denoted by t , t and t , respectivity. The transmission rate of infection through sufficient contact, from to , to and to were defined by and , respectively. The latent period of human infection was denoted by t and the transmission rate of infection through sufficient contact from to was denoted by .
The dynamic and transmissibility of this disease modeled by the following system of first-order differential equations : The transmissibility of asymptomatic infection was taken as ½ times of transmissibility of symptomatic infection, i.e. t, which was the same as influenza (Longini et al, 2005). Since 2.87 million peoples moves out from Wuhan city between January 10-24, 2020, therefore the moving rate is 0.2 million per day and the total population of Wuhan city at the end of 2018 was about 11 million (CBN, 2020& Wuhan Govt, 2020. Therefore, o . The relative shedding rate of in contrast to was also taken as 0.5. Initially, the prevalence of the virus in the market was taken as 1/100000. Since it is a positive single-stranded RNA virus, it cannot sustain in the external environment for long, howbeit, could stay in unknown host for 10 days (i.e. = 0.1). The estimated value of of SARS-CoV-2 was 2.2, where  applied intrinsic growth rate and serial intervals based method.

Susceptible-Exposed-Infectious-Recovered (SEIR) Model
The SEIR model was proposed by Tang et al. (2020a), the group studied the practical intercession of people's health and measures were also included. The data used in this model has been taken from WHO situation report, the National Health Commission of the People's Republic of China and the Health Commission of Wuhan City and Hubei Province (WHO, 2020d;WHO, 2020e). This researchbased on the determination of the dynamic and epidemiology status of the disease by calculating the basic reproduction number. Let the susceptible population is , exposed population is , the presymptomatic population is , the infected population is , the hospitalised population is and the recovered population is The quarantined susceptible, isolated exposed and isolated infected population is denoted by , and respectively. The transmission and dynamic of the virus are modelled by the following system of differential equations: In the simulation, the initial guess is taken as the data given on 10 January, 2020 from Health Commission of Hubei Province, is the number of subsequently recovered population which is 2.0, the number of quarantine population was 739 and set . The estimated reproduction number considered was 6.47 (Tang et al., 2020a).

Time-Dependant Dynamic Model (TDDM)
Tang and collaborators updated their SEIR model using the latest available data on January 23, 2020 (Tang et al., 2020b) and called this model as TDDM. In TDDM model, it has been assumed that the contact rate is time dependant variable and given by, Where initial contact is the rate on January 23, 2020, is the minimum contact rate by applying restrictions and control strategies, and denotes the exponential decreasing rate of contact rate.
The transition rate of symptomatic infected individuals to the quarantined infected class t has been taken as an increasing function with respect to time, t t t t t The governing differential equation of this model is the same as the governing differential equation of the previous model, the only difference is the term is replaced by t and c is replaced by c(t).
The effective daily reproduction number is defined by The same techniques and methods as in the SEIR model (Tang et al., 2020a) had been applied for simulating TDDM model. The estimated reproduction number by this study is 6.47. Lin et al. (2020) proposed the conceptual model where individual behavioral reaction and governmental actions were also included. Susceptible-Exposed-Infectious-Removed (SEIR) model has been carried out with two extra compartments, namely 'D' mimicking the public perception of risk regarding the 54 number of severe and critical cases and deaths, and 'C' represented the number of cumulative cases.

Conceptual model
The following system of differential equations are used for modeling (Lin et al., 2020), Where N is the total population, S, E, I, R denotes the susceptible, exposed, infected and removed population respectively, and t is the transmission rate that can be computed using the following relation,

t t
The basic reproduction number is calculated by employing next generation matrix approach and given by, In this model, the estimated value of is 2.8. Wu et al. (2020c) proposed the migration and emigration model based on the data from December 31, 2019, to January 28, 2020. In this study, they assumed that the virus transmission occurred due to the migration and emigration of people from Wuhan city, China. Hence, the virus can be exported internationally. Following SEIR model is used for Wuhan epidemic,

Migration & Emigration Model
The rate of international case exportation is defined by, The expected number of exportation case on day 'd' is calculated by, t t The maximum likelihood estimation for reproduction number is given by, Markov Chain Monte Carlo method was applied for calculating the basic reproductive number. They simulated the SEIR model by putting the value of (Wu et al., 2020c). Table 2 summarises and compares the five discussed COVID-19 transmission models and Fig. 10 presents their simulated results. The SEIR model by Tang et al. (2020a) and TDDM model by Tang et al. (2020b) give better prediction. The reproduction number (R0) estimated by these two model is highest among all the models which suggest that this outbreak could be more serious than predicted in other models.

Discussion and Conclusion
The deadliest pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), For identification by PoCT, a single blood sample is taken using puncturing the skin. It has been prophesized that the US will launch an all-time PoCT by the 30 th March 2020. In the case of the ICMR, they have employed MY LAB company's PathoDetect assay which aids in identifying the coronavirus pathogens in the infected patients.
Coronaviruses are large (diameter=~150-160 nm), round, bulbous, and pleiomorphic structures whose outer surface provides strength, rigidity and a definite shape. These belong to Nidovirales order and are enveloped single-stranded positive-strand RNA virus with a genome of~30kb. Human coronaviruses were first described in the 1960s and are said to have the onus for severe respiratory and gastrointestinal tract infections. The RNA viruses often carry selective packaging of their genomes and the first coronavirus packaging signal was studied thirty years back however, its preliminary functioning is still unclear. The packaging of coronavirus is quite a challenge to obtain a specific recognition and selection of gRNAs and other RNA species.
To understand the COVID-19 epidemic dynamics, several mathematical models were applied where basic reproduction number (R0) is computed by using Ordinary differential equations  (Wu et al. 2020c). Out of these models, the SEIR model and TDDM model give a better prediction. Further, the reproduction number estimated by these two models is highest among all the models which suggest that this outbreak could be more serious than predicted in other models.
Owing to the epidemic spreads, pharmacists and scientists around the globe are actively exploring drugs that would combat COVID-19 effectively. Till date, there is no specific medicine to prevent or treat COVID-19, however, antivirals such as interferon α (IFN-α), lopinavir/ritonavir, chloroquine phosphate, ribavirin, and arbidol are added in recent version of guidelines by the National Health Commission (NHC) of China as a tentative drug for the treatment of COVID-19. IFN-α is found effective against coronaviruses and reported to inhibit SARS-CoV reproduction in vitro. Further, in one of the recent studies, Chloroquine was found to block SARS-CoV-2 infection at lowmicromolar concentration, with a halfmaximal effective concentration of 1.13 μM and a half-cytotoxic concentration greater than 100 μM . Furthermore, Arbidol, an antiviral usually treats the influenza virus, can inhibit the infection of SARS-CoV-2 at a concentration of 10-30 µM (Dong et al., 2020). The efficacy and safety of these tentative drugs for COVID-19 is subjected to preclinical and clinical trials. For SARS-CoV-2, several potential vaccines, including recombinant attenuated viruses, live virus vectors, or mono viral proteins expressed from DNA plasmids, are available but none of them are yet approved. Vaccine generation for coronaviruses is an apex challenge to date. Since March 2020, many drug candidates have been subjected to clinical trials.