Coronavirus (Covid-19) Pandemic: Outbreak, Current Scenario, and Impact on Human Physiology In Pakistan

Coronavirus that is also known as COVID-19 disease is produced by SARSCoV-2. This causative agent is highly contagious and can cause potentially fatal pneumonia worldwide with serious public health concerns. In the beginning among infected individuals, most of them were those who were mainly shown to the wet animal market in a big city of China known as Wuhan. So, it was suggested that this was almost certainly the zoonotic source of COVID-19illness. The transitional source of origin and their mode of transmission to humans were not known obviously. Conversely, from human to human rapidly transformation have been confirmed generally. Currently, there is no availability of FDA approved clinically antiviral drugs and/or vaccines to be used against the COVID-19. Afterward, SARS-CoV and MERS-CoV, the occurrence of SARS-CoV-2 has been manifested as the third sketch of an enormously pathogenic coronavirus into human population globally. In this review, we provide a brief overview of the history of COVID-19 in Pakistan up-to 18th weeks after beginning, current situation, epidemiology, and its impact on the human population. Moreover, we focused on physiological variation during the incubation period, genome analysis of SARS-CoV2, supportive treatment approaches, and safety measures in the Pakistani population, which may be supportive for combating the risk of COVID-19 epidemic. We also reviewed the future approaches for the development of therapeutic interventions and vaccines to cope with the COVID-19 epidemic.


Introduction
Coronaviridae is a family of coronaviruses which belong to the order of Nidovirales. The crownish appearance of spikes on the virus' surface; therefore, it was known as a coronavirus [1]. The diameter of coronaviruses is approximately 65-125 nm and the capsid material of corona is containing a single-stranded RNA. The sub-categories of coronavirus are including alpha [α], beta [β], gamma [γ] and delta [δ] coronavirus. The genomic sequence of SARS-CoV-2 has shown a 99% similarity to the genome of SARS-CoV. Historically, SARS-CoV and MERS-CoV, H1N1, and H5N1 influenza-A are the main known epidemics causing acute respiratory distress and lung injury that can lead to pulmonary failure and leading to mortality and morbidity [2,3]. Coronaviruses were considered to infect only animals until 2002, when the world seen a SARS CoV's disease caused by SARS-CoV, in Guangdong, China [4,5].
SARS was ultimately controlled utilizing rapid isolation of patients; strict execution of infected person to quarantine along with their associates, inter-connecting of all person to person transmission is controlled, and all these precautionary measures successfully and efficiently eliminated the risk of SARS-CoV [6]. Recently during the last quarter of 2019, coronavirus which was named as novel coronavirus SARS-CoV-2, occurred in Wuhan, China, that have killed over a large population due to rapid spread of coronavirus infection [7]. To date 12 April 2020, COVID-19 is affecting 214 countries and territories all around the world. There are still a lot of un-known mechanisms associated with the COVID-19 outbreak; all these are causing severe illness and even subsequently several deaths, have been reported in China, the USA, Spain, Italy, Pakistan, and other worldwide countries [8]. In this minireview, we analyzed a brief overview about the history of COVID-19 new confirmed cases and death cases according to per weeks in Pakistan, Current situation of COVID-19 in Pakistan and countries comparison analysis of COVID-19 outbreak. Moreover, focused on physiological variation during different stages of incubation periods and WHO supportive treatment strategies and safety measure during SARS-CoV2 viral replication cycles, which may be supportive for combating the risk of COVID-19 epidemic. We also reviewed the future approaches for development of therapeutic interventions and vaccines to cope with the COVID-19 epidemic.

New confirmed cases of COVID-19 per weeks in Pakistan
In Pakistan, after the detection of the first 2 cases of COVID-19 on 26 Feb 2020 in Sindh Province, the number of coronavirus infected patients were gradually increased up to 8 th

Death cases of COVID-19 per weeks in Pakistan
The first death case was reported in 4 th week, Pakistan, a total of 7 no. of death cases were reported in this week, 3 in KPK and 4 death cases were declared in Punjab, Sindh, Baluchistan, and GB. Similarly, in the 5 th, 6 th , 7t, 8th, and 9 th weeks, the reported deaths were steadily increased up-to 19, 31, 50,102, 118 respectively. At the end of the 18 th weeks; a total of 4304 cases of death cases were announced ( Figure. 1B) [10,12]. birds, rabbits, snake, and marmots were frequently been sold and it is proposed that all these are the probably belong to the zoonotic origin of coronaviruses. The first report recognized that few species of bats and snakes which could be a potential source of coronaviruses. Only α and β sub-categories of coronaviruses can cause disease in humans, the feeding of infected animals mainly bats, and snakes are the main sources of food for chines peoples. And this route is the main source of virus transmission from animal to human due to close contact with the infected person; the virus is also transmitted to healthy people (Figure 2).Various surveys have recommended that human to human contact mainly by sneezing and coughing is a possible route for COVID-19 infection transmission [15].

COVID-19 Impact on human physiology
The incubation duration of COVID-19 is nearly 5 1/2 days and the symptoms of COVID-19 exhibit after the incubation period. The approximate duration from the appearance of the symptoms to death can range from 0 to 14 days [19].Mainly the duration is dependent on the patient's immunity and age. The impact of COVID-19 on human physiology was appearing in the forms of influenza, runny nose, coughing, fever, headache, dyspnea, diarrhea, shortness of breath and lymphopenia [20][21][22][23][24].Medical features exposed by a CT-scan of the chest were symbolized as pneumonia, contrariwise others infrequent sorts such as acute cardiac injury and acute respiratory distress syndrome prevalence; that led to death ( Figure.5) [25,26].

Structure and Genomic analysis of SARS CoV-2
The genomic sequence of the SARS-CoV-2 has been reported having more than 80% similarity to the previously detected human coronaviruses SARS-CoV [28]. The genome of SARS-CoV-2 comprises of10 open reading frames (ORFs). In SARS-CoV-2the biggest genes which encode the proteolytic processing (pp1ab) protein and 15 naps (non-structural proteins) for viral replication is ORF1ab gene [29,30]. In SARS-CoV and MERS-CoV, two pp1a and pp1ab polyproteins are translated into seventeen non-structural proteins (nsp1-nsp16), which form the transcriptase complex of viral replicas that initiates viral transcription and replication [31,32]. Similarly, SARS-CoV-2 ORFs on the 1/3 of the genome encode four core structural proteins such as spike (S), membrane (M), nucleocapsid (N), and envelope (E) proteins that may be involved in viral replication [33,34]. Accordingly, some previous investigations and few current studies showed that COVID-19 's genomic research associates the β-coronavirus genus ( Figure. 7) [35,36]. ORF genome, and some accessory proteins (37).

Supportive treatment and preventive measure against COVID-19 in Pakistan
There  Outcomes of continuing clinical trials are impatiently awaited. For preventive measures were essentially required to use gloves, eye protection, hand sanitizer, and N95 respirators for patients for medical staff along with all populations for safety, and also plenty of water and organ juice intakes are played a significant role for boosting up human immunity.

Future Prospects
Furthermost importantly working on human COVID- 19