COVID-19: A SYSTEMATIC REVIEW ON CORONA VIRUSHTML Full Text
COVID-19: A SYSTEMATIC REVIEW ON CORONA VIRUS
Ankur Choubey * 1 and Manushree Pachori 2
Surbhi College of Pharmacy 1, Sukhi Sewaniya, Bhopal - 462010, Madhya Pradesh, India.
Laxmi Narayan College of Pharmacy 2, Bhopal - 462022, Madhya Pradesh, India.
ABSTRACT: A novel coronavirus illness (COVID-19), activated by contamination with SARS-CoV-2, has frilled across 31 territories in China and more than 195 nations around the world. The change from the first side effects to intense respiratory trouble disorder (ARDS) is amazingly likely to be because of excessive cytokine discharge. There is a pivotal need to arrange sheltered and dynamic medications for activity. Chloroquine (CQ) presentations an inhibitory impact. In any case, the clinical utilization of CQ can cause serious reactions. Besides, hydroxyl chloroquine (HCQ) likewise shows an antiviral impact profoundly like that of CQ, restraining the cytokine storm by smothering T-cell enactment. Coronavirus immunization will be conveying after clinical preliminaries ahead in business sectors.
Coronavirus, Chloroquine, Vaccine, Hydroxychloroquine
INTRODUCTION: Coronavirus ailment (COVID-19) is an irresistible ailment brought about by a novel found in the first case in Wuhan, China, in December 2019. Various individuals tainted with the COVID-19 infection will encounter mellow to direct respiratory sickness and recoup without requiring uncommon treatment. Older and those with hidden clinical issues like cardiovascular infection, diabetes, ceaseless respiratory malady, and malignancy are bound to create genuine illness 1-4. The ideal approach to forestall and hinder transmission is being all around educated about the COVID-19 infection, the ailment it causes, and how it spreads. Shield yourself as well as other people from disease by washing your hands or utilizing a liquor based rub every now and again and not contacting your face 5.
The COVID-19 infection spreads principally through beads of salivation or release from the nose when a tainted individual hacks or sniffles, so it's significant that you additionally practice respiratory manners (for instance, by hacking into a flexed elbow). Right now, there are no particular immunizations or medicines for COVID-19. However, there are numerous progressing clinical preliminaries asses-sing potential treatments 6. The COVID-19 virus affects different people in different ways. COVID-19 is a respiratory disease, and most infected people will develop mild to moderate symptoms and recover without requiring special treatment.
People who have underlying medical conditions, and those over 60 years old have a higher risk of developing severe disease and deathz 7. Statistically, Coronavirus COVID-19 is affecting 196 countries and territories around the world, confirmed case 392440 with casualty 17159 while recovered 103,396 cases (Last updated: March 24, 2020, 12:35 GMT) 8, 9. Chloroquine and hydroxyl-chloroquine fight against COVID-19: Chloroquine is a quinine analogue medication used to prevent and to treat malaria in areas where malaria is known to be sensitive to its effects. Certain types of malaria, resistant strains, and complicated cases typically require different or additional medication. So, Chloroquine and Hydroxychloroquine have been available as weapons to fight against COVID-19. Repositioning of drugs for use as antiviral treatments is a critical need. It is commonly very badly perceived by virologists, as we experienced when reporting the effectiveness of azithromycin for the Zika virus. The response has come from China to the respiratory disease caused by the new Coronavirus (SARS- CoV-2) that emerged in December 2019 in this country. Indeed, following the very recent publication of results showing the in vitro activity of chloroquine against SARS-CoV-2, data have been reported on the efficacy of this drug in patients with SARS-CoV-2-related pneumonia (named COVID-19) at different levels of severity 10, 11.
Indeed, following the in vitro results, 20 clinical studies were launched in several Chinese hospitals. The first results obtained from more than 100 patients showed the superiority of chloroquine compared with the treatment of the control group in terms of reduction of exacerbation of pneumonia, duration of symptoms, and delay of viral clearance, all in the absence of severe side effects 12, 13. This has led China to include chloroquine in the recommendations regarding the prevention and treatment of COVID-19 pneumonia 14.
Coronavirus Vaccine: The present danger of avian-flu to the human populace, the potential for the reappearance of serious, intense respiratory disorder (SARS) - related Coronavirus and the distinguishing proof of numerous novel respiratory infections underline the need for the improvement of remedial and preventive procedures to battle the viral disease. Antibody improvement is a key segment in anticipation of broad viral contamination and in the decrease of grimness and mortality related to numerous viral diseases. In this part, Coronavirus immunization, particularly SARS-CoV antibodies, are, for the most part, discussed 15. Coronavirus vaccines can be inactivated Coronavirus, live attenuated Coronavirus, or S protein-based. Besides, there are still vectored vaccines, DNA vaccines, and combination vaccines against Coronaviruses.
Vaccines targeting several animal Co Vs. have been developed, and some have been demonstrated to be efficacious in preventing viral infection. However, a phenomenon of enhanced disease following vaccination has been observed in cats upon infection with feline infectious peritonitis virus following previous infection, vaccination, or passive transfer of antibody.
The phenomenon is not fully understood but is believed to be a result of enhanced uptake and spread of the virus through binding of virus- antibody immune complexes to Fc receptors on the surfaces of macrophages; low titer sub neutralizing antibodies directed against the S protein are mainly responsible.
Although antibody enhancement appears to be limited to feline infectious peritonitis virus among Co Vs., similar concerns have been raised with regard to SARS-CoV. Previously infected mice and hamsters are protected from subsequent infection with SARS-Co V in the absence of enhanced disease and vaccine studies, and passive immunoprophylaxis performed with mice and hamsters suggest that previous exposure and the presence of NAbs provide protection 16.
Inactivated Corona Virus Vaccine: The immune-genericity and efficacy of inactivated SARS-Co V vaccines have been established in experimental animals, and one such vaccine is being evaluated in a clinical trial. However, the development of inactivated vaccines requires the propagation of high titers of infectious virus, which in the case of SARS-CoV requires biosafety level 3-enhanced precautions and is a safety concern for production. Additionally, incomplete inactivation of the vaccine virus presents a potential public health threat.
Production workers are at risk for infection during handling of concentrated live SARS- CoV, incomplete virus inactivation may cause SARS outbreaks among the vaccinated populations, and some viral proteins may induce harmful immune or inflammatory responses, even causing SARS-like diseases 17.
Novel Corona Virus Related Information: Mers CoV Newmers Co V infection Novel Coronavirus 2012 (N Co V) Coronavirus Human coronavirus Coronavirus symptoms Novel Coronavirus infection New SARS-like virus Coronavirus treatment SARS coronavirus Spike protein Nucleo capsid Coronavirus replication Coronavirus hku1HCoV-EMC.
Live Attenuated Corona Virus Vaccine: To date, live attenuated vaccines for SARS-CoV have not been evaluated. However, systems have been developed to generate cDNAs encoding the genomes of CoVs, including SARS-CoV. The panel of cDNAs spanning the entire CoV genome can be systematically and directionally assembled by in-vitro ligation into a genome-length cDNA from which recombinant virus can be rescued. This system has been used for genetic analysis of SARS- Co V protein functions. It will enable researchers to engineer specific attenuating mutations or modifications into the genome of the virus to develop live attenuated vaccines. While live attenuated vaccines targeting respiratory viruses, including influenza viruses and adenoviruses, have been approved for use in humans, the observation that infectious virus is shed in the feces of SARS-Co V-infected individuals raises concerns that a live attenuated SARS-Co V vaccine strain may also be shed in feces, with potential to spread to unvaccinated individuals. Another concern is the risk of recombination of a live attenuated vaccine virus with wild-type Co V; however, there may be ways to engineer the genome of the vaccine virus to minimize this risk.
S-Protein-based Corona Virus Vaccine: The roles of S protein in receptor binding and membrane fusion indicate that vaccines based on the S protein could induce antibodies to block virus binding and fusion or neutralize virus infection. Among all structural proteins of SARS-Co V, S protein is the main antigenic component that is responsible for inducing host immune responses, neutralizing antibodies and/or protective immunity against virus infection. S protein has, therefore, been selected as an important target for vaccine and anti-viral development.
Although full-length S protein-based SARS vaccines can induce neutralizing antibody responses against SARS-CoV infection, they may also induce harmful immune responses that cause liver damage of the vaccinated animals or enhanced infection after challenge with homologous SARS-Co V, raising concerns about the safety and ultimate protective efficacy of vaccines that contain the full-length SARS-Co V S protein.
Vectored Vaccines against Corona Virus: Several groups have reported preclinical evaluation of vaccines utilizing other viruses as vectors for SARS-Co V proteins, including a chimeric par influenza virus, MVA, rabies virus, vesicular stomatitis virus (VSV) and adenovirus. Chimeric bovine / human par influenza virus 3 (BHPIV3), a live attenuated parainfluenza virus vaccine candidate, was utilized as a vector for the SARS-Co V structural proteins, including S, N, matrix (M) and envelope (E), alone or in combination. Studies with vectored vaccines further demonstrate that induction of S protein-specific NAbs is sufficient to confer protection.
DNA Vaccines against Coronavirus: DNA vaccines have demonstrated strong induction of immune responses to viral pathogens in animal models, specifically in mice; however, clinical data on DNA vaccines in human subjects are limited. DNA vaccines encoding the S, N, M, and E proteins of SARS-Co V have been evaluated in mice. Vaccination with S-, M, and N-encoding DNA vaccines induced both humoral and cellular immune responses, with some variation in the relative levels of induction. Combination vaccines against Coronavirus combination vaccines have also been evaluated for their ability to augment immune responses to SARS-Co V.
Administration of two doses of a DNA vaccine encoding the S protein, followed by immunization with an inactivated whole virus, was shown to be more immunogenic in mice than either vaccine type alone.
The combination vaccine induced both high humoral and cell-mediated immune responses. High NAb titers were also observed in mice vaccinated with a combination of S DNA vaccines and S peptide generated in Escherichia coli. Combination vaccines may enhance the efficacy of DNA vaccine candidates. The SARS-Co V vaccine strategies reported to date demonstrate that S protein-specific NAbs alone are sufficient to provide protection against viral challenge.
While SARS-Co V has not yet reemerged, its unknown reservoir leaves open the possibility that it, or a related virus, will again infect the human population. The development of vaccines targeting this virus will help, in the event of its reemergence, to potentially stop its spread before it wreaks the social and economic havoc caused by the previous outbreak. Furthermore, lessons learned from the generation of these vaccines may aid in the development of future vaccines against known and newly identified Coronaviruses.
Pharmacological Treatments with Potential Clinical Benefit:
Remdesivir (GS-5734): Remdesivir is an investigational monophosphoramidate prodrug of an adenosine analog that was developed by Gilead Sciences, Inc. in response to the Ebola outbreak in West Africa from 2014 2016. In its active triphosphate nucleoside form, remdesivir binds to RNA-dependent RNA polymerase and acts as an RNA-chain terminator.
It displays potent in-vitro activity against SARS-CoV-2 with an EC50 at 48 hours of 0.77 µM in Vero E6 cells. 3 Similarly, activities have been demonstrated against other zoonotic Coronaviruses with EC50 values of 0.07 µM demonstrated for both SARS-CoV-1 and MERS-CoV.
Remdesivir is highly selective for viral polymerases and is therefore expected to have a low propensity to cause human toxicity. Accordingly, Sheahan and colleagues demonstrated a wide therapeutic index for remdesivir in a human airway epithelial cell model 6.
The drug also displays a high genetic barrier to resistance in Coronaviruses and has a long intracellular half-life that allows for once-daily dosing. The dose under investigation for the treatment of COVID-19 is 200 mg intravenously (IV) on day 1 followed by 100 mg IV daily for up to 10 days, infused over 30-60 min.
Lopinavir / Ritonavir: Lopinavir is a human immunodeficiency virus 1 (HIV-1) protease inhibitor administered in fixed-dose combination with ritonavir (LPV/r), a potent CYP3A4 inhibitor that “boosts” lopinavir concentrations. Lopinavir appears to block the main protease of SARS-CoV-1, inhibiting viral replication.
In 2003, Chu and colleagues evaluated a series of antivirals for in-vitro activity against SARS-CoV-1. They reported lopinavir at 4 mg/mL, and ribavirin at 50 mg/mL inhibited SARS-CoV-1 after 48 h of incubation and that the agents were synergistic when used together. De Wilde and colleagues later described the antiviral activity of lopinavirus against SARS-CoV-1 and demonstrated an EC50 17.1 ± 1 in Vero E6 cells, which is near the upper range of LPV plasma concentrations previously measured in patients with HIV infected patients 24, 25.
Sheahan and colleagues evaluated the in-vitro efficacy of LPV/r in combination with interferon beta (INFb) against MERS-CoV and found the addition of LPV/r did not significantly enhance antiviral activity of INFb alone (EC50 =160 IU/mL vs. 175 IU/mL, respectively) 5. They also described the EC50 of LPV/r (8.5 µM) and LPV alone (11.6 µM), suggesting similar activity to that described for SARS CoV-1. Despite in-vitro activity against MERS-CoV, therapeutic doses of LPV/r + INFb in mice models failed to reduce virus titer and exacerbated lung disease.
This is notable as this was the same study where remdesivir demonstrated both more potent in-vitro activity as well as in-vivo efficacy. However, the in-vivo animal data for MERS- Co V appears equivocal given a nonhuman primate model demonstrated improved clinical and pathological features following LPV/r treatment. A randomized controlled trial of LPV/r and recombinant interferon-β1b versus placebo is currently enrolling for patients with MERS-CoV, which might help clarify the apparent discrepancy between in-vitro and animal models.
Nitazoxanide: Nitazoxanide has demonstrated potent in vitro activity against SARS CoV-2, with an EC50 at 48 h of 2.12 µM in Vero E6 cells. This potent activity is consistent with EC50 values for nitazoxanide and its active metabolite, tizoxanide, against MERS-CoV in LLC-MK 2 cells where EC50 values of 0.92 and 0.83 µM have been demonstrated, respectively. Nitazoxanide displays broad-spectrum in vitro antiviral activity against influenza, respiratory syncytial virus, par influenza, rotavirus, and norovirus, amongst others in addition to Coronaviruses.
This broad-spectrum antiviral activity is believed to be due to the fact that the mechanism of action is based on interference with host regulated pathways involved in viral replication rather than virus-specific pathways.
CONCLUSION: We epitomize all the potential interference for COVID-19 disease according to past medications of SARS and MERS. We have discovered that the general activities are indistinguishable critical to improve have an invulnerable answer against RNA viral contamination. The invulnerable reaction has frequently been demonstrated to be debilitated by deficient nourishment in many model frameworks, just as in human investigations. Be that as it may, the nourishing status of the host, until recently, has not been considered as a contributing element to the rise of irresistible viral sicknesses. Along these lines, we propose to confirm the nourishing status of COVID-19 tainted patients before the organization of generic medicines. Moreover, we likewise discovered Coronavirus explicit medicines and antiviral medications were exceptionally helpful for the treatment of SARS and MERS.
CONFLICTS OF INTEREST: Nil
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How to cite this article:
Choubey A and Pachori M: Covid-19: a systematic review on Corona virus. Int J Pharmacognosy 2020; 7(4): 96-00. doi link: http://dx.doi.org/10.13040/IJPSR.0975-8232.IJP.7(4).96-00.
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