PERCEPTION OF THE TREATMENT VACCINES FOR COVID-19 (CORONAVIRUS DISEASE-2019) – REVIEW ON CURRENT STATUS

PERCEPTION OF THE TREATMENT VACCINES FOR COVID-19 (CORONAVIRUS DISEASE-2019) - REVIEW ON CURRENT STATUS

Saritha Surapaneni

Department of Pharmacology, R. R. College of Pharmacy, Bangalore, Karnataka, India.

ABSTRACT: A Novel virus, coronavirus 2 (SARS-CoV-2), in 2019 from Wuhan, China which is globally expanded, causing the severe acute respiratory syndrome. Coronavirus is transmitted human to animal or human to human through airborne droplets. Coronavirus causes respiratory infections like pneumonia, cold, sneezing and coughing, while in animals, it causes diarrhoea and upper respiratory diseases. The virus outbreak has been declared a public health emergency of international concern by the World Health Organization (WHO), Since Covid -19 rapidly spread throughout the world from the Hunan seafood market at Wuhan, South China. The virus enters into the human cell through the membrane ACE-2 exopeptidase receptor. WHO and ECDC guided to stay away from a public place and close contact with contaminated individuals and pets. Coronavirus (2019-CoV), first and foremost, was isolated on 7th January 2020 at Wuhan market China. Here we have encapsulated the current clinical features data to guide budding Covid-19 about the Prevention, Diagnosis, Treatments and Prevention. Throughout the world, the disease has caused a range of degrees of sickness. The patient manifests various symptoms, usually Fever, Cough, Sore throat, Breathlessness, Fatigue. We collected the data from various, articles Research Report, and WHO guidelines in this review. It is necessary to give awareness to the readers that new data is updating nearly every hour regarding clinical characteristics, diagnosis, treatment strategies, and outcomes COVID-19. The disease is being treated through general treatment, symptomatic treatment, using some antiviral drugs, oxygen therapy and altering the immune system. WHO declared the SARS-Cov-2 virus in March 2020 as a global pandemic. It is necessary to identify the major causes and detach the suspected people from the confirmed cases of COVID-19 to prevent the possible transmission of infection to other patients and health care staff. It will be possible to assess this global disaster's full health, social and economic impact only when the pandemic ends. This review represents a picture of the current state of the treatment for Covid-19.

Keywords: Coronavirus disease-2019, COVID-19, MERS-CoV, SARS-CoV, WHO, Respiratory syndrome, Symptoms, SARAS, Treatment, Wuhan

INTRODUCTION: Coronavirus (Co V) that causes sickness to differ from common cold to more freezing disease such as Middle East.

Respiratory syndrome (MERS-Co V) and severe acute respiratory syndrome (SARS-Co V) belong to a large family of Zoonoses viruses ¹. In the Middle of 1930s, researcher establishes that these viruses can reason for respiratory tract infections ². In the past several years, 6 strains of coronaviruses were pointed out; yet, in 2019 December, the Latest strain has expanded across in Wuhan, China ³.Viral infections of the respiratory tract express to a weighty subject of human and individual comfort everywhere the world. These respiratory ailments unite the most normal complaint ⁴. Amongst the diverse respiratory contagions, corona infection is a substantial pathogen of individuals and beings. In corona contaminations, the coronavirus's maximum usually arrives at the URT (upper respiratory tract), where they display their effect of elementary colds. Be that as it may, these infections similarly affect the lower respiratory tract in the gradually helpless laypeople, where they can prompt pneumonia, asthma, respiratory sickness complaints or even SARS (Severe acute respiratory disorders) or MERS (Middle East respiratory disorders) ^{5, 6}. The World Health Organization elected as coronavirus disease 2019 (COVID-19)7.WHO acknowledged the outburst of worldwide pandemic COVID-19 with cases in more than 45 countries In late January 2020, which was scattering wild outdoor China, most expressively in South Korea, Italy and Iran with over 2,924 expiries and 85,212 cases inveterate while 39,537 improved on 29 February 2020, 06:05 AM (GMT) COVID-19 is a positive-sense single-stranded RNA virus (+ssRNA). Its RNA sequence is around 30,000 bases in length ⁸. The corona envelope (E) protein is a small, integral membrane protein involved in numerous features of the virus’ life cycle, such as pathogenesis, envelope formation, assembly, and budding, together with its connections with both other Co V proteins (M, N, and S) and host cell proteins (release of infectious particles after budding) ^{9, 13}. The infected person is considered with Fever, Upper respiratory tract symptoms, Lower respiratory tract symptoms, Diarrhoea, Lymphopenia, Thrombocytopenia within 3-6 days after exposure. Currently, there is no vaccine or approved treatment action for people, but Chinese traditional medicines, such as Shu Feng Jie Du capsules and Lianhuaqingwen capsules, could be probable treatments for COVID-19. Yet, there are no clinical trials compliment a ring the wellbeing and usefulness of these medicines ¹⁴. The key perception within all the boosters is the capability of the vaccine to initiate an immune response in a quicker mode than the pathogen itself. Although traditional vaccines, which depend on biochemical trials, induced potent neutralizing and protective responses in the immunized animals, they can be costly, allergenic, and time-consuming and necessitate in vitro culture of pathogenic viruses leading to the serious concern of safety ^{15, 16}. Thus, the essential for safe and competent vaccines is extreme lyre commended.

Types of Corona Human Corona Virus ¹⁷:

Variable Structure of Corona Virus: Coronavirus is wrapped in an envelope containing a large number of the spike of glycoprotein (S) a special round shape, positive Single-Stain RNA virus that infects population on wide Scale. The two scientists- Tyrell and Bynoe firstly portrayed the First Stain of coronavirus in early 1966 by taking the sample from the patients suffering from the common cold ¹⁸. Four subfamilies, coronaviruses exist, specifically Alpha, Beta, Gamma, Delta. Alpha-and beta-corona viruses start from bats, gamma-and delta-infections begin from pigs, and winged creature’s beta strains of coronavirus cause serious infection and fatalities to the population. Alpha stains show asymptomatic or sometimes symptomatic contamination. This all genome shows a large difference between size, one is 26 kb, and another is 32 kb.COVID-19 has a place with the B heredity of the beta-corona viruses and has a similar identity with the SARS-CoV infection ^{19, 20}. The four basic qualities encode the protein that is spike protein (S) present on the spike of the virus, a film protein (SM), layered glycoprotein (M) and the nucleocapsid protein (M) In the beta coronavirus-HCoV-OC43 and beta coronavirus-HKU1. The entire genome level of a bat coronavirus is 96% similar to coronaviruses-19 (SARS-CoV-19) ²⁰. Because of its crown-like structure on their surface that's why it's known as coronavirus. "corona" means "radiance" or "crown"(Latin). This infection can spread through human-to-human transmission, the researcher now affirmed that. However, the first wellspring of the infection has not been recognized. A flare-up of coronavirus disease-19 (COVID-19) contamination In December 2019 started in Wuhan, the capital of focal China's Hubei area ²¹. While the infection likely identified with the city's Huanan Seafood Market, across the board, human-to-human transmission has brought about 73,451 cases in 26 nations with 1,875 passings as of February 18, 202022-26. On 20 January 2020, this disorder become the first particular within the United States, and all outnumber of instances within the USA has reached 15 as on February 17, 2020 ^{26, 27}.

Spread and Incubation Period Corona Virus: The Hubei Province neighbourhood government on February 22. has been accounted that hatching time is of 27 days and the JAMA investigation of 5 cases with a hatching time of 19 days was seen distributed on February 21 and the current incubation period for the novel coronavirus COVID-19 is 2-14 days ^{28, 29}. The spread of coronavirus is mainly from one person to person. Among population- health individuals who are easily exposed within 5-6 feet distance to an infected individual. Respiratory droplets are delivered from the infected person to the healthy individual when they sneeze, cough, wheeze. These droplets can get transferred into the entrance of other healthy individuals who have close contact with a person infected with coronaviruses. The virus replicates in the ciliated epithelium that causes cellular damage and infection at site of infection. Angiotensin-converting enzyme 2 (ACE.2), a membrane exopeptidase in the receptor used by coronavirus in entry to human cells, according to a study published in 2019, ^{30, 32}.

Signs and Symptoms of Corona Virus: According to a report published on 24 January 2020, corona virus-infected patient has many common features such as fever, cough, fatigue while diarrhoea and dyspnoea were found to be an as uncommon feature. Many of the patient-reported bilateral abnormalities. Coronavirus was isolated from bronchoalveolar lavage fluid in China in 2020. It is also detected in blood samples. Till now, coronavirus was not confirmed in faeces and urine samples of patent ^{33, 35}. The Emergency Committee of WHO asserted this epidemic as a worldwide health emergency on 30, Jan of 2020 ³⁶ dependent on developing case warning rates in Chinese and universal areas. The case discovery rate is changing hourly and day by day. About 20% of cases are serious, and mortality is around 3% ³⁷. After the 2-14 days presented to coronavirus, the side effect and sigh/symptom may be seeming and can include ³⁸. Mostly includes Fever, Cough, Shortness of breath, Pneumonia in both lungs, Headache, Muscle soreness, Fatigue.

Diagnosis for the Corona Virus: For detection of coronavirus 2019, a sample from respiratory tract-like swab from the nasopharyngeal region, from the throat, aspirate of nasal and content of nasal washing is taken from the suspected patients within the 3-4 days when they show symptom of sickness. (In this period, the infected person can shedding virus) ³⁹. Sample Collection: This is the following method that a laboratory takes a sample for testing of coronavirus: Swab test: From the nostril or throat of the infected patients, a health professional takes sample by swiping the special type of the swab.

Nasal aspirate for taking a sample from the nasal, health professional injects a saline solution or normal saline (NS solution) to the nasal of the infected patients and then remove the solution with suction and collect the sample. Tracheal aspirate: In this procedure, a bronchoscope, which is a light, thin flexible tube, is inserted to the mouth of the patients or maybe to the lungs by a health professional and collects the sample for examination. Sputum test: For the collection of sputum from the lungs, a health professional asks to cough for collection of the sputum in a special sputum cup or a special type of swab. Sputum is a viscous material produced by the lungs in response to some allergy material blood Coronavirus can also be diagnosis by blood sample for detection of antigen-antibody reaction test. The health care professional takes a blood sample from the patient’s artery or vein from his/her arm. The FDA approves more extensive usage of rapid test kits for recognition of corona virus. This method is fast, accurate for the detection of the virus. This test is used for the detection of COVID-19 in CDC-approved laboratories in the world. Virus isolated in cell culture and tested for the Polymerase chain reaction (PCR) assay that is more practical and available commercially. Serological method for testing antibodies in the blood ³⁹.

Prevention and Risk Management Involved: There is no treatment or vaccine for treating the ongoing coronavirus COVID-19, but USA and UK perform a clinical trial on the vaccine of coronavirus. People with COVID-19 should receive supportive care to help relieve symptoms. For severe cases, treatment should include care to support vital organ functions. An individual who assumes they'll be uncovered to COVID-19 must contact their healthcare provider right now. The excellent manner to save your illness is to avoid being uncovered to this virus. But, as a reminder, CDC usually recommends regular preventive moves to assist save you the unfold of breathing diseases, consisting of. Do not come in contact with the infected individual. Keep away from touching your eyes, nostril, and mouth. Stay at home when you are unwell. Cover your mouth and nose while sneezing or coughing with a clean tissue and throw or put it into bin having a lid. Clean and sterilize the gadgets and areas that contact an infected individual with a normal household cleansing agent or wipes. Washing hands with soap and water properly for 10-20 sec or using sanitizer with 70% alcohol. Avoid sharing dishes, glasses, bedding, and other household gadgets in case you're ill. Clean and disinfect surfaces you frequently touch.

Discussion on Current Treatment and Vaccines Updates: There is no special vaccine for this yet. Only supportive therapy is the treatment strategy followed by health professionals. Supportive therapy includes administration of antipyretic and analgesic, hydration, mechanical ventilation as respiratory support, and antibiotic use in bacterial infections. Some research studies claimed that ribavirin and interferon-alpha had offered ³⁹. As of 8 April 2020, the global COVID-19 vaccine R&D landscape includes 115 vaccine candidates, of which 78 are confirmed as active, and 37 are unconfirmed (development status cannot be determined from publicly available or proprietary information sources). Of the 78 confirmed active projects, 73 are currently at exploratory or preclinical stages. The most advanced candidates have recently moved into clinical development, including mRNA-1273 from Moderna, Ad5-nCoV from Can Sino Biologicals, INO-4800 from Inovio, and LV-SMENP-DC pathogen-specific aAPC from Shenzhen Geno-Immune Medical Institute. Numerous other vaccine developers have indicated plans to initiate human testing in 2020.

A striking feature of the vaccine development landscape for COVID-19 is the range of technology platforms being evaluated, including nucleic acid (DNA and RNA), virus-like particles, peptide, viral vector (replicating and non-replicating), recombinant protein, live attenuated virus, and inactivated virus approaches. Many of these platforms are not currently the basis for licensed vaccines, but experience in fields such as oncology is encouraging developers to exploit the opportunities that next-generation approaches offer for increased speed of development and manufacture. It is conceivable that some vaccine platforms may be better suited to specific population subtypes (such as the elderly, children, pregnant women or immune-compromised patients).

Considering the candidates, the novel platforms based on DNA or mRNA offer great flexibility in terms of antigen manipulation and potential for speed. Indeed, Moderna started clinical testing of its mRNA-based vaccine mRNA-1273 just 2 months after sequence identification. Vaccines based on viral vectors offer a high level of protein expression and long-term stability and induce strong immune responses. However, it is unclear how different forms and/or variants of the S protein used in different candidates relate to each other or the disease's genomic epidemiology. Experience with SARS vaccine development indicates the potential for immune enhancement effects of different antigens, a topic of debate and could be relevant to vaccine advancement.

Profile of vaccine developer of the confirmed active vaccine candidates, 56 (72%) are being developed by private/industry developers. The remaining 22 (28%) of projects are led by academic, public sector, and other non-profit organizations. Although many large multinational vaccine developers (such as Janssen, Sanofi, Pfizer and GlaxoSmithKline) have engaged in COVID-19 vaccine development, many lead developers are small and/or inexperienced in large-scale vaccine manufacture.

So, it will be important to ensure coordination of vaccine manufacturing and supply capability and capacity to meet demand. Most COVID-19 vaccine development activity is in North America, with 36 (46%) developers of the confirmed active vaccine candidates compared with 14 (18%) in China, 14 (18%) in Asia (excluding China) and Australia, and 14 (18%) in Europe. Additional vaccine development efforts have been reported for China, and CEPI is in dialogue with the Chinese Ministry of Science and Technology to confirm their status. Lead developers of active COVID-19 vaccine candidates are distributed across 19 countries, which collectively account for over three-quarters of the global population. However, there is currently no public information on vaccine development activity in Africa or Latin America, although vaccine manufacturing capacity and regulatory frameworks exist in these regions.

The epidemiology of COVID-19 might differ by geography, and it is likely that effective control of the pandemic will require greater coordination and involvement of the southern hemisphere in vaccine R&D efforts. Outlook The global vaccine R&D effort in response to the COVID-19 pandemic is unprecedented in terms of scale and speed. Given the imperative for speed, there is an indication that vaccines could be available under emergency use or similar protocols by early 2021. This would represent a fundamental step-change from the traditional vaccine development pathway, which takes on average over 10 years, even compared with the accelerated 5-year timescale for the development of the first Ebola vaccine, and will necessitate novel vaccine development paradigms involving parallel and adaptive development phases, innovative regulatory processes and scaling manufacturing capacity. Industry benchmarks for Traditional vaccine development paradigms cite attrition rates for licensed vaccines of more than 90%. The approaches being applied for COVID-19 development - which involves a new virus target and often novel vaccine technology platforms and novel development paradigms as well - are likely to increase the risks associated with delivering a licensed vaccine and will require careful evaluation of effectiveness and safety at each step. In order to assess vaccine efficacy, COVID-19-specific animal models are being developed, including ACE2-transgenic mice, hamsters, ferrets and non-human primates. Bio safety-level 3 containment measures are needed for animal studies involving live-virus challenges and the demand for these capabilities is likely to require international coordination to ensure that sufficient laboratory capacity is available. Finally, strong international coordination and cooperation between vaccine developers, regulators, policymakers, funders, public health bodies, and governments will be needed to ensure that promising late-stage vaccine candidates can be manufactured in sufficient quantities and equitably supplied to all affected areas particularly low-resource regions. CEPI has recently issued a call for funding to support global COVID-19 vaccine development efforts guided by three imperatives: speed, manufacture, and deployment at scale, and global access. We maintain a dynamic portfolio management approach and will make our enabling science resources available globally. We urge the global vaccine community to collectively mobilize the technical and financial support needed to successfully address the COVID-19 pandemic through a global vaccination program and provide a strong base to tackle future pandemics ⁴⁰.

The first U.S. patients have been dosed in a phase 2/3 clinical trial testing whether a lead messenger RNA (mRNA) vaccine candidate can prevent infection with the virus that causes COVID-19.NYU Grossman School of Medicine, under the auspices of NYU Lang one Health’s Vaccine Center, served as one of the original sites for the initial stages of the same study that focused on the vaccine’s safety and if it was tolerated well. The next phase - 2/3 - for which NYU Grossman School of Medicine will also participate as 1 of 120 centers, may enroll up to 30,000 healthy Participants aged 18 to 85 globally. The study will measure whether the vaccine candidate can protect against COVID-19 infection with severe acutere respiratory syndrome coronavirus 2 (SARS-CoV-2). Pfizer Inc. and Bio N Tech SE today announced the trial’s transition into its final stage. Vaccine designers at Bio N Tech sought to determine which protein components of SARS-CoV-2 were “most noticed by” the human immune system, with the goal of teaching the system to further attack them upon a future encounter with the virus, researchers say. “It is tremendously encouraging to see the early phase of this trial succeed and to have a lead candidate emerge for global testing,” says Mark J. Mulligan, MD, director of the Division of Infectious Diseases and Immunology and the Vaccine Center at NYU Lang one. “We will continue to engage in rigorous scientific study to learn as soon as possible if this vaccine can be part of the public health solution to this terrible pandemic.” NYU Lang was chosen as a trial center because of Dr. Mulligan’s expertise in infectious disease research programs that have over decades assessed investigational vaccines for HIV and several other viruses, including Zika, Ebola and pandemic influenza.

The study vaccine is part of the class called “mRNA vaccines” that, with recent advances, can quickly be computer-designed and scaled up into millions of doses if successful and pending regulatory approval using high-speed technologies. RNA-based vaccines also provide a level of safety since it is not possible to catch SARS-CoV-2 virus or COVID-19 disease from the RNA vaccines themselves. Earlier trial phase successful mRNA vaccines are based on RNA, or ribonucleic acid, a form of genetic material similar to DNA. Human cells use mRNA to translate DNA instructions into proteins, the workhorse molecules that makeup cell structures.

In the pandemic coronavirus, RNA serves as the primary genetic material instead of DNA. Two of the study vaccine candidates in phase 1 of the trial contained viral RNA encoding the “spike proteins” used by SARS-CoV-2 to attach to proteins on human cell surfaces, the first step in invading the cells in which it multiplies. Including the spikes in vaccines has the potential to make proteins required for viral survival (ability to infect) visible to the human immune system, say the investigators. For this reason, the lead vaccine to move forward into the larger trial, BNT162b2, will encode an optimized SARS-CoV-2 full-length spike glycoprotein, at a 30-µg dose level in a 2-dose regimen. Such vaccine injections are delivered in small segments of mRNA encoding spike protein into the arm muscles of participants. All vaccine versions are encased in a fatty lipid particle meant to prevent their destruction by enzymes and let them persist long enough to enter the cytoplasm of cells in muscle and nearby lymph nodes. Once there, the spike protein is made and triggers the production of antibodies, immune proteins that specifically glom onto this viral target protein, disabling it and tagging it for removal from the body. The current ongoing clinical trial began with a phase 1/2A study on May 4, 2020. The company reported that subjects that received 2 doses of either 10 or 30 µg of BNT162b2 expressing the SARS-CoV-2 spike protein had significantly elevated spike-binding antibodies at day 28 (7 days after dose 2). Also, 7 days after dose 2, all subjects who received 10 or 30 µg of BNT162b2 had SARS-CoV-2 “neutralizing antibodies,” capable of defending cells from the virus and blocking its biological effects.

Local reactions and systemic side effects after immunization were dose-dependent, generally mild to moderate, and short-lived. The company reported no serious adverse events. The phase 2/3 trial is designed as a 1:1 vaccine candidate to placebo, randomized, observer-blinded study to obtain safety, immune response, and efficacy data needed for regulatory review. Suppose the ongoing studies are successful and the vaccine candidate receives regulatory approval. In that case, the companies expect to manufacture up to 100 million doses by the end of 2020 and potentially more than 1.3 billion doses by the end of 2021. On July 22, the U.S. government placed an initial order of 100 million doses for $1.95 billion, with the right to acquire up to 500 million additional doses from company ⁴¹.

CONCLUSION: In an unexpected pandemic, the rapid development of vaccines and relative testing on coronavirus has been challenging for all pharmaceutical companies and the government. Moreover, clinical trials play a key role in evaluating the hit molecules and provide adequate safety and efficacy, unfortunately, till now, we have not found any treatment for the coronavirus other than social distancing as primary care. The government has implemented the chain break reactions and clear rules of implementation for the citizens to be aware of the spread and necessary care need to be taken for the seniors and who suffer from respiratory tract infections. Finally, hope we receive a vaccine in the very near future to reduce the mortality rate.

ACKNOWLEDGEMENT: The authors would like to express their gratitude to Mr. Raja Reddy, Chairman and Mrs. Kiran Reddy, Secretary, Dr. Narayana Swamy, Principal, R R College of Pharmacy, Bangalore, India, for providing the necessary facilities and support to carry out the work.

CONFLICTS OF INTEREST: The author declares that there are no competing interests.

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    How to cite this article:

    Surapaneni S.: Perception of the treatment vaccines for covid-19 (coronavirus disease-2019) - review on current status. Int J Pharm Sci & Res 2021; 12(9): 4676-83. doi: 10.13040/IJPSR.0975-8232.12(9).4676-83.

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