Determining the Efficacy of Available Treatments and Containment Measures against SARS-CoV-2

Over the past 20 years, outbreaks related to coronavirus-associated diseases, such as MERS and SARS, have been threatening the whole world. The novel coronavirus emerged in Wuhan, China and belongs to the SARS family. It has been named “Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)”. Keeping in view the history of pandemics faced by the world, it would be fair to say that each of them has been one of its kind, bringing an equal amount of distress and damage to the humanity. With the help of other countries, Pakistan has coped well with the pandemic. Measures taken by different countries included curfews imposed in Italy, Spain, Russia, and India, while the UK, Ireland, and China opted for a more passive approach. South Korea imposed strict self-isolation requirements across the country, whereas UAE suspended all ferry services from Iran. Vaccines authorized by FDA to treat COVID-19 include Pfizer manufactured by Biotech which has 95% efficiency, Moderna with 94% efficiency, and Johnson and Johnson which has an overall efficiency of 72% and 86% efficiency in case of severe infection. These stats are from the USA. Whereas, vaccines such as Sinopharm, Sinovac, CanSino-Bio, and Sputnik have been administered in Pakistan following their approval by the Drug Regulatory Authority of Pakistan (DRAP). This study aims to review the various aspects of the COVID-19 pandemic such as disease symptoms, the mode of action, a brief comparison of control measures taken by different countries, therapeutic trials to cure COVID-19, and the status of vaccines.


INTRODUCTION
In December 2019, a pneumonia-like infection was discovered in Wuhan, China. The likely origin site, Huanan Seafood Wholesale Market, was immediately sealed. In Wuhan, social distancing was rigidly enforced before being applied everywhere else. All kinds of social events, including the Lunar New Year celebrations, were put on hold by the Chinese government. The WHO dubbed the new * Corresponding Author: humaira.6127@wum.edu.pk infection as COVID-19 and categorized it as a pandemic in January 2020 [1].

Symptoms
The symptoms of COVID-19 start to appear within 2-14 days after exposure to the virus. It is not necessary that people infected by COVID-19 show all the symptoms of the disease. Indeed, some people remain asymptomatic or their symptoms vary from mild to severe. In line with CDC, symptoms comprise headache, cold or fever, fatigue, sore throat, cough, BioScientific Review Volume 5 Issue 1, 2023 shortness of breath, aches in muscles or body, loss of taste or smell, diarrhea or vomiting, and congestion. People with a prior illness or old age can develop severe health issues because of COVID-19.

Adequacy of Health Systems
Inadequate health facilities have led to a high mortality rate due to various pandemics across the world. Many people lose their lives in pandemics due to neglecting infectious diseases and lack of preparation on behalf of the healthcare system. Multiple kinds of studies have been conducted on SARS-CoV-2 to learn more about it and the effects it has on the society, the economy, and the health system. The COVID- 19 pandemic has caused immeasurable human suffering and deaths, disrupted social relations, and deprived people of their livelihoods and prosperity [2]. New and reemerging infectious diseases have been occurring at an uncommon pace. According to the World Health Organization (WHO), more than 20 infectious diseases have been a source of pandemics all over the globe in the preceding decade [3]. A number of these calamities have been brought [4] on by infectious diseases like H1N1 and MERS.
Recently, COVID-19 pandemic has prompted the researchers to understand the science of emerging organisms and human vulnerability to their risks, creating successful measures to overcome them. Recognizing these issues, on the other hand, is the first step in a well-prepared planning process that would help to ensure the best possible public health protection [5].
Researchers suggest that because of the history of responding to other disease outbreaks, fragile and fragmented health systems, and lack of health knowledge, the government of Pakistan and all relevant agencies should remain vigilant and be fully prepared to respond to abnormal situations [6].

Strategies Developed by Different Countries
With remarkable speed and resource mobilization, the world has responded to the COVID-19 pandemic. Within a few weeks, Chinese scientists identified and sequenced the causative agent of this pandemic. To date, considerable genomic and clinical data have been exchanged rapidly around the world. Several possible treatments have been suggested for this disease [7]. In the worst-affected countries, the virus wreaked havoc on healthcare services, causing shortages of medical equipment, medication, and sanitary supplies.
More research must be conducted in an innovative laboratory to stop emergency conditions created by countless viruses that reside in nature and have not yet been found or named [8]. Although a coping mechanism cannot be pre-defined for such unprecedented scenarios, different countries may deal with it differently in their unique ways. Strategies have been developed to successfully halt virus transmission that disrupt daily life and economic functioning, prompting officials to take rapid steps to ameliorate their negative impacts. During the pandemic, governments throughout the globe strived to help people cope with the economic and social effects of the lockdown by providing support and compassionate measures for employees and employers. [9].
China, the center of the outbreak, took drastic steps which included lockdowns, bans on traveling, and the closure of theatres, sporting events, and public spaces. South Korea imposed strict self-isolation requirements across the Department of Life Sciences Volume 5 Issue 1, 2023 country, with fines or a possible jail term facing those who break them. UAE suspended all ferry services from Iran and demanded a health statement from all the crew members working in ports 72 hours before their arrival. In Singapore, text and web-based solutions were introduced that required restrictions for patients in home quarantine through which they could share their whereabouts with the government [10].

Therapeutic Trials to Cure COVID-19
There is a lot of curiosity about whether drug therapies can be used to prevent COVID-19, although it remains unclear which drugs, if any, are successful. The evidence for hydroxychloroquine is the subject of the first version of the guideline. A panel of international guidelines indicates that hydroxychloroquine is no longer a high priority for research and other promising drugs should be inquired about for their function in the prohibition of COVID-19 [11].
Many therapeutic trials are being conducted to reduce viral transmission, morbidity, and mortality [12]. The only antiviral approved to date is remdesivir. It is a nucleoside analog known for its in vitro role against RNA viruses and ebolavirus. It reduces the recovery time in patients with serious COVID-19. In animal experiments, it was administered to a mouse that was already infected with SARS-CoV-2. The results showed a lower virus titer as compared to the control group, improvement in the damaged lung tissues, and better treatment as compared to interferon-beta combined with lopinavir/ritonavir. Three common approaches are used to discover antivirals effective against SARS-CoV-2. Testing existing antiviral drugs, which are broad spectrum and accustomed to treating other viral diseases, is the first method. By exploiting standard assays, the result of these drugs on plaque constitution, cytopathy, and pseudo coronavirus can be measured. Interferon-II and Interferon-I were identified by using this methodology. The second method comprises a drug repurposing program [13]. It is a method of drug discovery based on the illustration of a novel treatment for COVID-19 by using the chemical library of previously known compounds that can be at the preclinical stage [12]. The chemical library includes data about transcription properties in distinct cell lines. This method was used to identify various drugs with immunological and anatomical implications, such as influencing estrogen receptors, sterol or lipid metabolism, neurotransmitter regulation, kinase signal transfer, DNA synthesis or repair, and protein processing. The third method is based on the redevelopment of novel drugs by exploiting biophysical and genome comprehension of individual SARS-CoV-2 genome [13]. Instead of investing time and cost in the denovo elaboration of new drugs, it is better to repurpose the existing drugs to cure COVID-19. Antiviral drugs may show an inadequate response in patients with an austere disease. The reason is the production of CRS (cytokine release syndrome). To halt CRS and virus replication, the fusion of immunomodulators and combination of antivirals are used respectively as treatments. Such fusion and combination comprise the potential therapeutic solution for severe COVID-19 infection [14].
Data that provides evidence regarding the efficacy of these methods is still scarce [15]. There is a requirement to validate the safety and effectiveness of these drugs through clinical trials [13]. RCT (randomized controlled trial) is critical in determining the effectiveness and safety of new therapies. The critical problem is the groups that show low representation and it must be addressed. Due to this problem in trials, the advantages of remdesivir cannot be generalized; therefore, patient recruitment should be a key goal. A small, non-randomized, open-label study was performed in China to estimate the effect of favipiravir on non-severe COVID- 19

Virology of COVID-19 and Drug Therapies
An enveloped ssRNA virus SARS-CoV-2 binds spike protein to the host's ACE2 (angiotensin-converting enzyme 2) receptor upon entry into the cell through receptors on the host cell and endosomes. TMPRSS2, a host transmembrane serine protease assists in viral entry. After entry, it controls the host machinery to synthesize viral glycoproteins that form a transcriptase-replicate complex. Structural proteins play an important function in the assembly and release of virions [16].

CONCLUSION
The pandemic brought on by the SARS-CoV-2 infection was dubbed COVID-19 by the World Health Organization (WHO). There are numerous vaccines available that protect against the SARS-CoV-2 infection, although there are no widely available effective antiviral medications for COVID-19 caused by SARS-CoV-2.
Remdesivir has simultaneously been approved by many nations as the first treatment for COVID-19. The requirement of a COVID-19 vaccination that is both safe and effective is widely acknowledged as essential in the containment of the pandemic. The difficulties and work required to quickly design, assess, and deliver something at scale are significant. So, all the available vaccines should be evaluated to know which are effective against the disease.