Global Pandemic Conditions and List of Possible Medications and Vaccines for the Treatment of COVID-19: A Review

At the end of December 2019, a novel coronavirus was identified which caused severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with a disease known as coronavirus disease 2019 (COVID-19). The virus first originated in the city of Wuhan in China, causing symptoms such as pneumonic plague, which began in the Wuhan region and then spread throughout the world with high transmission efficiency. Special precautions and care are needed such as leaving the public area, covering your mouth with a mask, not shaking hands, washing hands, and sanitation from time to time. Infection due to SARS-CoV-2 shows several symptoms, one of which is very often the patient shows difficulty breathing. Currently, COVID-19 has been declared a global pandemic and has almost attacked all countries in the world, including in India which has one of the largest human populations in the entire world. One of the challenges in handling COVID-19 is the unavailability of drugs or special vaccines to treat the disease, so clinical practitioners and academics are currently testing various drugs to see how they affect the COVID-19 patients. Some of the drugs tested provide effective mechanisms against SARS-CoV-2, such as chloroquine, remdesivir, lopinavir, and vaccines under development, showing efficacy to inhibit SARS-CoV-2 infection in vitro. These drugs are still being tested and are now at the forefront to combat the effects of SARS-CoV2 infection. This review article will discuss all kinds of ins and outs of SARS-CoV-2 and COVID-19, including the transmission method, how to prevent it, as well as various drugs and vaccines currently used in handling COVID-19.


INTRODUCTION
Novel coronavirus 2019 (nCoV-2019) are cover, positivesense single-stranded RNA viruses with a nucleocapsid of helical symmetry. Viruses that cause the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have widely been known to cause respiratory and intestinal infections in humans after the outbreak of "severe acute respiratory syndrome" or SARS, also known as Coronavirus disease or COVID-19 (Zumla et al., 2016;Cui et al., 2019;Li et al., 2020). The causative coronavirus of this outbreak was named SARS-CoV-2 due to its resemblance to SARS-CoV. The SARS-CoV-2 infects ciliated bronchial epithelial cells and type-II pneumocytes via angiotensin-converting enzyme 2 (ACE2) as a receptor, while MERS infects unconditional bronchial epithelial cells and type-II pneumocytes using dipeptidyl peptidase 4 (DPP4) also known as CD26 as a receptor Rockx et al., 2020).
The mechanism related to the SARS-CoV-2 infection is still unclear. However, structural analysis shows the possibility of the virus entering human cells through several pathways, one of which is ACE2 receptors Astuti & Ysrafil, 2020). This newly emerged virus has much more similarity with SARS-CoV than MERS-CoV, thus both SARS-CoV and SARS-CoV-2 may cause pathogenesis through similar mechanisms transmission of SARS-CoV to humans Khan et al., 2020a). Due to this COVID-19 all over the world face pandemic conditions (Khan et al., 2020b).
This review article will discuss all kinds of ins and outs of SARS-CoV-2 and COVID-19, including the transmission method, how to prevent it, as well as various drugs and vaccines currently used in handling COVID-19. Also, this article discusses the statistical impact of COVID-19 on several countries, especially in India. This article also discusses information regarding the handling of COVID-19 specifically in India, including the inspection location of SARS-CoV-2 samples that are spread throughout all regions of India. It is hoped that this review article will provide actual information regarding the current condition of the impact of COVID-19 and the therapies that are being developed to handle it.

STRUCTURE AND PROTEIN FUNCTION
In general, the structure and function of proteins from SARS-CoV-2 have similarities with other coronavirus families such as SARS-CoV and MERS-CoV although SARS-CoV-2 was found to infect more human beings than either of its predecessors (Pal et al., 2020). There are five main proteins in SARS-CoV-2 that play an important role related to the nature of pathogens in humans, consisting of the nucleocapsid (N), spike (S), viral envelope (E), and membrane protein (M), as well as hemagglutinin esterase (HgE) (Walls et al., 2020). The function of each protein is presented in Table I, while the structural illustration of SARS-CoV-2 as reported by Khan et al. (2020b) is presented in Figure 1.

Symptoms of COVID-19
In general, COVID-19 can affect anyone, young or old, male or female, in all parts of the world. However, the symptoms shown between individuals are not always the same (Yi et al., 2020). Some individuals with certain conditions show a tendency for more severe symptoms and need treatment in hospitals, while some people do not cause clinical symptoms at all. This disease also causes more symptoms in the elderly and people with special underlying health conditions such as the presence of certain congenital diseases (Singhal, 2020). However,  .

Prevention of COVID-19 infection
The SARS-CoV-2 is known to be transmitted directly from human to human. At this point, the best way to prevent the spread of COVID-19 is to minimize direct contact with other humans (Yuen et al., 2020). Some ways can be done, including avoiding traveling outside the house or to public places if there is no urgent need, taking a safe distance of several meters with others if forced to interact, and increasing the body's immune system by routinely exercising and consuming various vitamins (Ali & Alharbi, 2020). The following are some precautions that can be taken to prevent or minimize the spread of COVID-19, including: 1. Wash your hands thoroughly with soap and water for at least 20 seconds.
2. Avoiding touching the nose, mouth, eyes, or other parts of the face except after washing hands or using a hand sanitizer.
3. Use hand sanitizers that contain antiseptics such as alcohol with at least a 70% concentration if soap and water are not available 4. Maintain a safe distance of at least 2 meters from others, especially those who are coughing and sneezing.
5. Avoid public places as much as possible, especially those that do not allow to maintain a safe distance such as traditional markets, public transportation, and others. 6. Avoid close contact with people who are sick with any disease, especially those who are undergoing treatment at the hospital (Omer et al., 2020).
Elderly aged over 65 years must fully avoid traveling outside the house because of a higher risk of infection. This is related to the immune system that has begun to decline, so it is necessary to take more intensive precautions to avoid being infected with COVID-19. In general, the principles of prevention of transmission of COVID-19 are stated by WHO as physical distancing, which is as much as possible to keep a safe distance from others (Djalante et al., 2020).

Mode of transmission COVID-19
In general, a typical symptom of COVID-19 is a respiratory infection that is transmitted through respiratory droplets. The SARS-CoV-2 can spread between people who are close by through respiratory droplets or direct contact routes that were previously in contact with droplets . Transmission from a droplet when someone makes close contact within a distance of 1 meter or less with someone who coughs or sneezes can be inhaled directly through the nose or mouth, especially if the person is not wearing a mask or face shield (Guner et al., 2020). Therefore, in addition to maintaining a safe distance, protecting the mouth, nose, and eyes from possible exposure to respiratory droplets is also mandatory, especially in areas known to have positive cases of COVID-19 (Liu et al., 2020a). In addition to being transmitted directly through droplets, a person can also be infected if it touches the surface of an object that has been exposed to droplets containing SARS-CoV-2 for some time. SARS-CoV-2 itself is known to have a long lifetime on several surfaces of the object, so washing hands becomes mandatory after touching the surface of any object. Also, you can use waterproof gloves when on the move and take it off when it touches the face (Morawska & Cao, 2020). The incubation period for COVID-19 itself varies between individuals, with an average of five to six days and can be as long as 14 days (Lauer et al., 2020).

TREATMENT OF COVID-19
Chloroquine Chloroquine is a quinoline compound that has a structure similar to quinine, an alkaloid compound found in the Chinchona sp. plant, and used as an antimalarial drug. The US uses chloroquine as one of the treatment options for COVID-19. Its use has been approved by the FDA to be tested as a treatment for COVID-19. Chloroquine is being tested in various clinical trials conducted by government agencies and academic institutions. Chloroquine is known to inhibit viral infections by increasing the endosomal pH needed for viral/cell fusion, inhibiting entry through changes in glycosylation of ACE2 receptors and spike proteins (Megarbane, 2020;Wang et al., 2020d).

Hydroxychloroquine
Hydroxychloroquine is a hydroxy derivative of chloroquine which has antimalarial activity such as chloroquine but with fewer side effects. Like chloroquine, hydroxychloroquine inhibits entry of SARS-CoV-2 through changing the glycosylation of receptors-ACE2 and spike protein viruses (Gautret et al., 2020;Liu et al., 2020b).

Teicoplanin
Teicoplanin is an antibiotic (glycopeptide) marketed by Sanofi-Aventis routinely used to treatment of bacterial infection. it was found to be active in vitro against SARS-CoV, has joined the list of molecules that could be used as 4 therapeutic arsenals against COVID-19. According to the current study showed that this activity was conserved on SARS-CoV-2 (the target sequence that serves as the cleavage site for cathepsin L is conserved among SARS-CoV spike protein). Based on data of teicoplanin usage in the treatment of infectious diseases, with further newly investigation of the antiviral effect of this molecule on SARS-CoV-2 and suggest teicoplanin as another potential alternative for the treatment of COVID-19. Teicoplanin works by inhibiting cell wall synthesis (Baron et al., 2020).

Favilavir
Favilavir is an antiviral medication used to treat influenza in Japan, being developed and manufactured by Toyama Chemical and used as a treatment for coronavirus in Japan. Favilavir or favipiravir was formerly called fapilavir. The drug has reportedly shown efficacy in treating the disease with minimum side effects in a clinical trial with 70 patients. The clinical trial is being conducted in Shenzhen, Guangdong province (Zhai et al., 2020).

Lopinavir-ritonavir
The combination of lopinavir and ritonavir (also known as Kaletra) developed by AbbVie, Inc. was originally designed to treat HIV. In the clinical trial, the patient was 54 years old and was given a combination of these two drugs and had a significant source of reduction in his SARS-CoV-2 levels . However, a recent report by Cao et al. (2020)  to 55 years will be registered for the study (Doremalen et al., 2020).

AdCOVID
AdCOVID is a single-dose, intranasal vaccine candidate

TZLS-501
TZLS-501 is a monoclonal antibody for the treatment of

Novel Coronavirus developed by Tiziana Life Sciences.
This monoclonal antibody is a human IL-6R (anti-interleukin-6 receptor). TZLS-501 prevents lung damage and increases IL-6 levels. This drug works by binding to IL-6R and depleting the amount of IL-6 that circulates in the body, thereby inhibiting chronic lung inflammation (Tiziana Life Sciences, 2020; Duddu, 2020).

OYA1
OYA1 is an antiviral compound developed by OyaGen, Inc. and has strong antiviral activity against coronavirus in the laboratory-based assays against the coronaviruses SARS-CoV-2 and MERS-CoV and also is a dual targetspecific antiviral against filoviruses such as Ebola virus. It was found to be more effective in inhibiting SARS-CoV-2 from replication in cell culture. OYA1 is planned to be further investigated to determine the efficacy of treating coronavirus (Pawar, 2020).

BPI-002
BPI-002 by BeyondSpring, Inc. is a novel orally administered small molecule agent that is a potent T-cell

BXT-25
BXT-25 is an anti-necrosis drug that carries oxygen to tissues when the flow of blood is blocked. BXT-25 has been developed by Bioxytran, Inc. as a treatment for Acute Respiratory Distress Syndrome (ARDS) in latestage patients infected with the SARS-CoV-2. The drug may help in transport oxygen to the vital organs and enable the patient to recover and survive. The treatment will allegedly offer enough time for the patient to recover and, over time, the body's immune system will destroy the virus (Bioxytran, 2020;Duddu, 2020).

Kevzara or sarilumab developed by Regeneron
Pharmaceuticals-Sanofi is a fully human monoclonal antibody, in phase two leading to three clinical trials in patients with severe COVID-19 infection. Kevzara is approved for the treatment of rheumatoid arthritis and is known to block the interleukin-6 (IL-6) pathway, which causes an overactive inflammatory response in the lungs of COVID-19 patients (Regeneron Pharmaceuticals, 2020; Magro, 2020;Duddu, 2020).

SNG001 developed by Synairgen Research is the IFN-β-
1a formulation for direct delivery to the lungs through nebulization. This is a neutral pH and free of mannitol, arginine, albumin, and human serum, making it suitable for direct inhalation delivery to the active site. SNG001 can be proven to have an important role in the current outbreak COVID-19 epidemic, especially concerning high-risk populations very affected by this virus and the like (Synairgen Research, 2020;Mantlo et al., 2020;Duddu, 2020).