Available online on 15.08.2021 at http://jddtonline.info

Journal of Drug Delivery and Therapeutics

Open Access to Pharmaceutical and Medical Research

Copyright  © 2021 The  Author(s): This is an open-access article distributed under the terms of the CC BY-NC 4.0 which permits unrestricted use, distribution, and reproduction in any medium for non-commercial use provided the original author and source are credited

Open Access  Full Text Article                                                                                                                                         Review Article 

A Review on the Novel Corona Virus with International and Indian Perspective

Gayatri Suresh K P*, Thabit Ahmed**, Mohamed Abdelgadir Mohammed Saeed*, Jereish Varghese Daivamthadathil*, Anandhu Jayan***, Jerin Reji Samuel***

*PharmD Interns, Bangalore Baptist Hospital, Bellary road, Bangalore, Karnataka, India

**Cardiologist, Consultant, Bangalore Baptist Hospital, Bellary road, Bangalore, Karnataka, India

***PharmD students, Bangalore Baptist Hospital, Bellary road, Bangalore, Karnataka, India

Introduction 

Common flu and Covid 19

Corona viruses as the name suggests are called so due to the crown-like projections on their surfaces. "Corona" in Latin means "halo" or "crown." first identified in the 1960s, followed by   SARS-Co V IN 2003, HCo V- NL63 in 2004, HKU1 in 2005, MERS-CoV in 2012 respectively. The human corona viruses are currently classified into seven types, which include, HCoV-229E, HCoV-OC43, HCoV-NL63, SARS-CoV, HKU1, MERS-CoV and 2019-nCoV. The corona virus (MERS-CoV and SARS-CoV) are more dangerous among all the coronaviruses. ⁴ COVID-19 and influenza have a similar clinical presentation since they both cause respiratory disease and primarily both viruses are transmitted by contact, droplets and fomites^5 6

SARS CoV-2

Corona viruses have naturally and evolutionarily, shaped and hosted by the bats. Indeed, it is postulated that most of the corona viruses that are found in humans are derived from the bat reservoir. ⁷The recent studies have confirmed the genetic similarity of SARS-CoV-2 and a bat beta corona virus of the sub-genus Sarbecovirus. ^7,8

The genome sequence of the novel corona virus is 96.2% similar to the bat SARS-related coronavirus (SARSr-CoV; RaTG13) collected from Yunnan province, China, but is not similar to the genomes of SARS-CoV (about 79%) or MERS-CoV (about 50%). It is been confirmed that the SARS-CoV-2 uses the same receptor, the angiotensin-converting enzyme II (ACE2), same as that of SARS-CoV. But the route of transmission from natural reservoirs to humans remains blinded, studies have been showing the pangolins providing a partial spike gene to SARS-CoV-2. (the crucial functional sites in the protein of SAR-CoV-2 are identical to one of the viruses that were isolated from a pangolin). ^7,9

Aetiology and pathophysiology

CoVs are positive-stranded RNA viruses that have a spikey appearance due to the presence of glycoproteins on the outer surface. It belongs to the family   Coronaviridae, which has the subclass Orthocoronavirinae that classifies the viruses into four genera of CoVs that include Alphacoronavirus (alphaCoV), Betacoronavirus (betaCoV), Deltacoronavirus (deltaCoV), and Gammacoronavirus (gammaCoV). ¹⁰¹¹

The  SARS-CoV-2 belongs to the betaCoVs category. It has a round/elliptical structure with a pleomorphic form. It has a diameter of  60–140 nm. This novel corona virus is sensitive to ultraviolet rays and heat and also these viruses can get inactivated by lipid solvents that include ether (75%), ethanol, chlorine-containing disinfectant, peroxyacetic acid and chloroform except for chlorhexidine. ^10,12

Virion   structure

Coronavirus virus mainly contains 4 structural proteins,i.e spike (S), membrane (M), envelope (E), and nucleocapsid (N) proteins,   which are all encoded within the 3′ end of the viral genome.

S protein: The S protein with a mass of∼150 kDa uses an N-terminal signal sequence to gain access to the ER and is heavily N-linked glycosylated. The spikey structure on the surface of the virus is due to the encodement of the homotrimers. ^11,13. It is a trimeric S glycoprotein that is a class I fusion protein that mediates the attachment to the host receptor. In some coronaviruses, S is cleaved by a host cell into two separate polypeptides noted S1 and S2. S1 forms the large receptor-binding domain of the S protein and S2 forms the stalk of the spike molecule. ¹¹

M protein: It is small in mass with ∼25–30 kDa and has 3 transmembrane domains and is observed to give the virion its shape. ¹¹

E protein: The E protein has a mass of ∼8–12 kDa and is found in small quantities. E protein in coronaviruses are specifically different but have a common architecture. The significant topology of E protein is not completely studied but data suggest that it is a transmembrane protein. ¹¹

Patients infected with COVID-19 had higher leukocyte numbers, high blood levels of cytokines and chemokines, increased levels of plasma pro-inflammatory cytokines and abnormal respiratory findings. The common symptoms included dry cough, coarse breathing sounds of both lungs, body temperature, fever, sore throat and fatigue. ¹⁴

The pathogenesis of COVID-19 infection being a respiratory system targeting virus is considered to be severe pneumonia, RNA anaemia, along with the incidence of ground-glass opacities, and acute cardiac injury. ¹⁵

Clinical presentation and transmission

Incubation period

The incubation period for COVID-19 is observed to vary between 7-14 days, with a median time of 4-5 days from exposure to symptoms onset. Certain studies have reported 97.5% of patients with COVID-19 are developing symptoms within 11.5 days of SARS-CoV-2 infection. ¹⁶

Clinical symptoms

The prevalence of symptoms of COVID 19, based on over 55,000 lab cases shows fever(88%) , dry cough(67%),sore throat (14%) and fatigue(38%).COVID 19 is more contagious and less severe when compared to other SARS & MERS.¹⁴

Implications of mutations on the virus

Over 1year & 6 months, 1200 variants of the novel coronavirus have been identified, of which 1000 strains have been studied. ¹⁷The current scenario rates 11 mutations per sample, which accounts for more than the national average (8.4) and the global average(7.3).¹⁸

Scientists have observed three major mutations of the COVID-19 virus so far:

• D614G
• VUI2020-12/01
• N501Y

D614G was responsible for the fast spread of the virus in Europe, the US and the rest of the world. VUI 2020-12/01 and N501Y are the current ones spreading in the UK. And the  'South Africa drift', where three mutations happened in the genetic make-up of the virus.¹⁹Also, B.1.167 Covid variant being recognised as Singapore strain is believed to affect the younger children.²⁰

Currently, the exponential increase of the cases in India is attributed to the mutations -L452R, E484Q, and P681R. with other mutations being recognised over as: 

Another variant Delta (B.1.617.2), belongs to a viral lineage first recognised in India during the second wave, that seemed to be around 60% more transmissible than the already highly infectious Alpha variant (also called B.1.1.7). Delta is found to be partially resistant to vaccines, A study published on 22 May found that a single dose of either AstraZeneca's or Pfizer's vaccine reduced a person’s risk of developing COVID-19 symptoms caused by the Delta variant by 33%, compared to 50% for the Alpha variant. A second dose of the AstraZeneca vaccine boosted protection against Delta to 60% (compared to 66% against Alpha), while two doses of Pfizer’s jab were 88% effective (compared to 93% against Alpha).²¹²²

Treatment approaches & failure 

Lopinavir and Ritonavir

Lopinavir and ritonavir (Kaletra) was given to those adult patients with laboratory-confirmed SARS-CoV-2 infection with certain criteria were eligible to receive lopinavir/ritonavir for 14 days after being confirmed with  (i) respiratory distress with respiratory rate ≥22/min or SpO₂ of <94 per cent; (ii) lung parenchymal infiltrates on chest X-ray; (iii) hypotension defined as systolic blood pressure <90 mmHg or need for vasopressor/inotropic medication; (iv) new-onset organ dysfunction, (v) age >60 yr, diabetes mellitus, renal failure, chronic lung disease and immune-compromised patients. Patients were monitored to document clinical, laboratory and safety outcomes. ²³ 

Failure 

In a few of the studies conducted it is concluded that in hospitalized adult patients with severe Covid-19, there was no benefit with lopinavir-ritonavir treatment beyond standard care. ²⁴   Also according to the literature, it states that there was no significance in the treatment of Kaletra with COVID-19, only that there was an improvement of 1 day earlier of recovery. ²⁵

Tocilizumab

Recommended the use of tocilizumab as a single intravenous dose of 8 mg/kg of actual body weight which can be increased up to 800 mg given in combination with dexamethasone (6 mg daily)in certain hospitalized patients who are exhibiting rapid respiratory decompensation due to COVID-19.

Failure 

Tocilizumab (Actemra) did not reduce severe respiratory symptoms, intensive care visits, or death any better than standard treatments, the Italian Medicines Agency. ²⁶

Remdesivir 

recommended using remdesivir for patients who were on high-flow oxygen, mechanical ventilation, or ECMO.²⁷

Failure 

studies report that in patients with covid 19 who were administered with remdesivir, the patients’ developed bradycardia along with signs of worsening QT interval. This reverted upon stopping remdesvir therapy. The prevalence of bradycardia with prolonged QT interval is not well-known yet with this medication.²⁸

Ivermectin

Studies done in vitro suggested that ivermectin acts by inhibiting the host importin alpha/beta-1 nuclear transport proteins, that is a vital intracellular transport process where viruses hijack to enhance infection thereby suppressing the host’s antiviral response and also ivermectin acts by interfering with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein to the human cell membrane. Ivermectin is said to be host-directed based on its broad-spectrum activity in vitro against the viruses that cause other major viral infections. some studies show that ivermectin has a potential anti-inflammatory property, which has been postulated to be beneficial in people with COVID-19.²⁹

Failure 

The small size of the study, the unclear treatment arm assignments, and the lack of accounting of disease severity at baseline make it difficult to conclude the efficacy of using IVM to treat patients with mild COVID-19.³⁰

Current treatment

Vaccinations put forward 

*mRNA vaccines teach our cells how to make a protein—or even just a piece of a protein—that triggers an immune response inside our bodies.³¹

Johnson & Johnson’s Janssen COVID-19 Vaccine: CDC and FDA have recommended a pause in the use of Johnson & Johnson’s J&J/Janssen COVID-19 Vaccine in the United States out of an abundance of caution as people who have received the J&J/Janssen COVID-19 Vaccine within the past three weeks developed severe headache, abdominal pain, leg pain, or shortness of breath should seek medical care right away.³⁴

Vaccination and Incidence of infection

During the initial implementation phases, as for every new vaccine, post-introduction evaluations will be important to address many of the remaining questions about the performance of these vaccines. When a vaccine is used outside trial populations the effects of the vaccine may differ in specific geographies or subpopulations. Vaccine effectiveness (VE) might be different against various disease outcomes, against infection and infectiousness, and newly emerging virus variant strains. Additionally, important programmatic issues will need to be addressed, such as the effectiveness of incomplete dose schedules, variation in dose intervals, and the interchangeability of different vaccine products. Suboptimal cold chain capacity, and off-schedule and incomplete delivery of doses could lead to different vaccine performances. Vaccines might not be as effective against new variants. Finally, assessing the duration of vaccine protection requires longer-term studies.³⁵

Complications of Covid 19

In population about 1 in 6, have been found to show complications. Many of these complications may be caused by a condition known as cytokine release syndrome or a cytokine storm. This is when an infection triggers your immune system to flood your bloodstream with inflammatory proteins called cytokines. They can kill tissue and damage your organs, including your lungs, heart, and kidneys.³⁶

COVID-19 complications may include Acute Respiratory Failure, Pneumonia, Acute Respiratory Distress Syndrome (ARDS), Acute Liver Injury, Acute Cardiac Injury, Secondary Infection, Acute Kidney Injury, Septic Shock, Disseminated Intravascular Coagulation, Blood Clots, Multisystem Inflammatory Syndrome in Children, Chronic Fatigue, Rhabdomyolysis.^36 37

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