Overview of an Emerging Coronavirus Infection, COVID-19: Current Status of Vaccine Development and Therapeutics

Coronavirus infectious disease 2019 (COVID-19) first reported in Wuhan, China, causes serious respiratory illnesses such as lung failure and pneumonia. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) the pathogenic agent of COVID-19 has been confirmed as a novel coronavirus. WHO announced COVID-19 a global pandemic and now the whole world is eagerly waiting for vaccines and therapeutic treatment to get rid of this un-stoppable coronavirus. As COVID-19 infection, a global threat creates un-wanted human casualties and serious economic loss. To stop the ongoing uncontrolled situation researchers are racing to develop prevention and treatment strategies. Vaccines of different countries are in clinical and preclinical trials and the repurposed-drugs are providing to find out a positive result against COVID-19. The report is an analysis of published information focusing on treatment options including vaccination, drug-therapy, cyto-kines, therapeutic antibodies. Most of the vaccine’s development strategies and drugs target the surface structural spike glycoprotein or S-protein, the major inducer of pathogenic responses. Here, it is reviewed the features of SARS-CoV-2 and the global current status of therapeutic, and vaccine development for the prevention and effective treatment of COVID-19.

Health authorities in China reported to the World Health Organization (WHO) on 31 December 2019, a cluster of viral pneumonia cases of unknown cause responsible for respiratory infection in Wuhan, Hubei, and an investigation was started in early January 2020 [4]. As 7818 cases confirmed globally by Coronavirus Disease (COVID-19) the WHO declared the outbreak a Public Health Emergency of International Concern (PHEIC) on 30 January [5]. On March 12 th , 2020, the WHO declared the epidemic of COVID-19 as a pandemic [6]. The outbreak of COVID-19 that began in Wuhan in China in December last year has now turned into a pandemic. At present, more than 200 countries have confirmed cases of the virus. Most of us have not experienced anything similar to the current situation. The virus has struck with unprecedented scale and ferocity. Educational institutions, shops, restaurants, recreational facilities, and many others are closed for a few months or more. Our lives have almost come to a halt. All these are done for a very good reason-to retard the spread of the virus.
The COVID-19 crisis has played out in ways that have not been anticipated from the prevailing nature of governance in different countries. Governments and health care systems almost in all affected countries caught short-handed. For the prevention and control of COVID-19, many nations and communities around the world are trying their best to implementation of appropriate strategies.
Nothing certain treatment and prevention strategies like antiviral drugs or vaccines are available for human and animal coronavirus infections [7]. During Ebola, Zika, and Nipah various vaccines, drug options, and immunotherapeutic have been explored [8]. The safety, efficacy, and potency of previously explored drugs, vaccines and other treatment options in the above-mentioned diseases can play a vital role to discover valuable modalities for tackling the emerging COVID-19 [9] [10]. Until the development of vaccines or discovery of any treatment option we cannot halt the new, deadly, and highly infectious coronavirus disease, COVID-19, which has brought much of the world to a locked-down situation and standstill [11].

Epidemiology
First now the global threat SARS-CoV-2, a newly discovered coronavirus closely related to bat coronaviruses, pangolin coronaviruses in the phylogenetic tree  [12]. SARS-CoV and MERS-CoV are very much similar to SARS-CoV-2 according to the genomic sequence. Since its first reported case in late 2019, the infection has spread to other regions in China and other countries, and the transmission rate, the mortality rate, and the clinical manifestation slowly emerged. It will take time, we completely characterize the transmission pattern, pathogenesis, symptoms, origin, and immune response of the SARS-CoV-2 virus [2]. As of July 12, 2020, a total of 13,028,182 confirmed COVID-19 positive cases reported at least in 213 countries and territories around the world with an approximately 4.38% of fatality rate (571,080/13,028,182) [13]. The mortality rate 4.38% of SARS-CoV-2 [13] is lower than that of SARS-CoV (10%) [14] or MERS-CoV (37.1%) [15] but the infection rate and the number are about 10 times higher than others. Transmission of SARS CoV-2 from mild, moderate, severely symptomatic, or asymptomatic persons to persons is reported in many published reports [16]. Similar to the case for SARS-CoV and MERS-CoV are similar in origin [15], as 96% genome sequence is identical to bat coronaviruses like bat CoV, BatCoV RaTG13 so the bat is considered the probable origin of SARS-CoV-2 [15]. As with SARS and MERS coronavirus, SARS-CoV-2 is predicted to commonly pass through intermediate hosts, such as civets or camels, before leaping to humans though scientific consensus is that COVID-19 has a natural origin [17] [18].

General Clinical Features of COVID-19
A wide range of clinical manifestations is seen in SARS-CoV-2-infected patients for example-mild, moderately severe to rapidly progressive state with particular organ dysfunction.

SARS-CoV-2 Molecular Biology
Define Coronaviruses (CoVs) are single-stranded and enveloped positive-sense 5'-3' RNA virus belonging to the Coronaviridae family, which originally found in various species of birds, bats, snakes, and other mammals [29]. 229E, HKU1, NL63, and OC43 were the previously known coronaviruses strains that infected humans in various ways [30]. The latest SARS CoV-2 is also an enveloped, sin-

Factors of Virus (SARS-CoV-2) Transmission
The SARS CoV-2 is transmitted from person to person by some environmental, physical, and biological means including air, inanimate surfaces, hands, temperature, water and sewage, humidity, wind speed, food, and insects [40] [41] [42]. 1) Droplet transmission densely occurs when a person is coughing or sneezing with respiratory symptoms and other persons are in close contact (within 1 m) and is therefore at risk of having his/her mucosae (mouth and nose) or conjunctiva (eyes) exposed to potentially infective respiratory droplets. Respiratory infections can be transmitted through droplets of different sizes: when the droplet particles are >5 -10 μm in diameter they are referred to as respiratory droplets, and when they are <5 μm in diameter, they are referred to as droplet nuclei. According to current evidence, the COVID-19 virus is primarily transmitted between people through respiratory droplets and contact routes [40]. Transmission may also occur through fomites in the immediate environment around the infected person [41].
2) Airborne transmission occurs when microbes (SARS CoV-2) in droplet nuclei particles and particle size less than 5 μm in diameter can easily float in the air for a long duration of time and transmit from one area to another area [41]. The airborne transmission was not significant in an analysis of 75,465 COVID-19 cases in China [42].
3) SARS-CoV-2 may also transmit through feces because COVID-19 may lead to intestinal infection and viruses may be present in feces and this transmission is proved with evidence in some studies. In the meantime, a single study has found the COVID-19 virus by microbe culture from an infected person's stool specimen [43]. 4) Recent study report confirmed the presence of the SARS-CoV-2 virus in water and sewage. Even in the low prevalence of the virus, it is present in the wastewater which indicates the survival capacity of the SARS-CoV-2 virus in the sewage [44] [45].

Vaccines
The whole world is eagerly waiting for vaccines as it the only effective strategy 1) Recombinant Subunit Vaccine: Generally, subunit vaccines boost the immune system and act against the specific pathogenic virus without introducing that virus into the host body and it is highly safe with fewer side effects [16].
Clover Biopharmaceuticals is running a recombinant subunit vaccine pre-clinical trial for COVID-19 by targeting the trimeric S protein (S-Trimer) of the SARS-CoV-2. The University of Queensland is using a transformative technology called "molecular clamp "for developing subunit vaccines and they also implement GSK's adjuvant system in their effective vaccine development process [46].

Convalescent Plasma (CP) Therapy
For the prevention and treatment of infectious diseases, many countries allow convalescent plasma (CP) immunotherapy. During SARS, MERS, and H1N1 infection CP has shown effective immune response and boosted immunity against these infectious diseases [52] [53]. Neutralizing antibody containing plasma is taken from a donor who has recently recovered from this special type of infection. This extracted plasma is then administered to infected patients. Ongoing clinical reported that severe or critically ill COVID-19 patients who received CP therapy showed significant improvement in their health conditions [54]. Furthermore, other researches are conducting to identify specific characterized antibodies found in the recovered patient's plasma. Also trying to develop monoclonal antibodies for the treatment of COCVID-19, China and other countries approved convalescent plasma therapy specifically antibody therapy [53].

Drug Repurposing for COVID-19
Previously used antiviral drugs can be used as an effective treatment for symp-   [53]. • Remdesivir (GS-5734): Remdesivir, a broad-spectrum nucleotide analog antiviral prodrug, acts against many RNA viruses. It has been proved effective against SARS-CoV, MERS-CoV, and SARS-CoV-2 in preclinical trials by inhibiting replication of the virus. A report of randomized, placebo-controlled, double-blind, multicenter clinical trial of remdesivir in 237 patients in Hubei, China, has just been published. In this published report, there were no statistically significant clinical benefits except reduction in time to symptomatic clinical improvement [60]. Another study reported that the first COVID-19 confirmed patient's condition in the USA was improved on the 8 th day after hospitalization after receiving remdesivir therapy for seven days without any noticeable adverse effects [26].

Non-Pharmacological Interventions
Still, there are no vaccines or specific confirmed pharmacological interventions or therapy available to minimize or stop the rapidly transmitting of SARS-CoV-2 around the world [58]. We are on the very verge of vaccines discovery but until vaccines are marketed and available for all classes of people globally, we have to consider some effective non-pharmacological interventions (NPI) for COVID-19 treatment. Implementation of non-pharmacological interventions (NPI) such as early case identification and isolation, travel restrictions, vigilant contact tracing of potential secondary cases and bans, physical ("social") distancing, regular hand washing, stringent contact reductions, and improved hygiene [38]. Some approaches like non-necessary public spaces should be closed, services and facilities should be reduced, quality digital learning facilities for educational institutions should be encouraged, and self-isolation/work from or inside the home should be inspired. If these NPIs strategies are implemented as early as possible the deadly viral transmission could be minimized [53].

Summary
In this review report authors would like to provide an overview of published different information about the Corona Virus Infectious Disease 2019 (COVID- 19) which is a global threat. Here molecular biology of the SARS-CoV-2 virus and prevention as well as treatment strategies of COVID-19 is described in brief.
Zoonotic origin beta-coronavirus SARS-CoV-2 caused severe casualties in every sphere of human life globally. Now it is the prime concern to slow down the focusing on such experiences and advances as made with earlier SARS-and MERS-CoVs, which together could enable efforts to halt this emerging virus infection. We are hopeful that soon this world will be freed from the terrible clutches of COVID-19 and nature will regain its vitality.