Literature DB >> 34179072

A Minireview of the Promising Drugs and Vaccines in Pipeline for the Treatment of COVID-19 and Current Update on Clinical Trials.

Jeyanthi Venkadapathi1, Venkat Kumar Govindarajan2, Saravanan Sekaran3, Santhi Venkatapathy4.   

Abstract

The COVID-19 is affecting thousands of peoples day by day and continues to spread across the world. The present review has focused on promising repurposing drugs, including remdesivir, lopinvar/retinovar, favipiravir, hydroxychloroquine, monoclonal antibodies and vaccines against the SARS-CoV-2 infection. Besides, our review has also focused on many organizations that are in the race to develop vaccines using various approaches including DNA, RNA, viral vectors and subunit proteins against this highly contagious respiratory disease. The spike protein is being studied by scientists all over the world to develop potential vaccines. The antiviral drugs, antibodies and vaccines developed by various researchers around the world have entered clinical trials in humans. The current clinical trials for antiviral agents and vaccines with promising outcomes are being discussed. So far, four vaccines developed by the Pfizer-BioNTech vaccine, the Johnson and Johnson vaccine and two AstraZeneca vaccines (produced by SKBio in the Republic of Korea and Serum Institute of India) are approved by the World Health Organization for public use.
Copyright © 2021 Venkadapathi, Govindarajan, Sekaran and Venkatapathy.

Entities:  

Keywords:  COVID-19; antiviral drugs; clinical trial; update; vaccines

Year:  2021        PMID: 34179072      PMCID: PMC8219860          DOI: 10.3389/fmolb.2021.637378

Source DB:  PubMed          Journal:  Front Mol Biosci        ISSN: 2296-889X


Introduction

The current outbreak of COVID-19 (Coronavirus disease-19) has created a major health problem worldwide. The respiratory tract infection caused by the novel coronavirus strain known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which was first identified in Wuhan, China at the end of 2019 and quickly spread across the world within a short period. (Shereen et al., 2020). As of april 11, 2021, the virus has killed 2, 941, 533 people around the world (CSSE, 2021). The World Health Organization (WHO) on March 11, 2020, has declared the SARS-CoV-2 outbreak a global pandemic. Due to the lack of successful vaccine candidates or antiviral molecules, the infection and mortality rate have increased globally (Umesh and Yadav, 2021). The WHO, European Medicines Agency (EMA), United States Food and Drug Administration (FDA), the Chinese Government and drug manufacturers have collaborated with various academic and industry researchers to improve the development of vaccines, antiviral drugs, and post-infection therapies. The most important target proteins for SARS-CoV-2 include papain-like protease, RNA-dependent RNA polymerase, helicase, S protein, and ADP-ribose diphosphatase (Venkat Kumar et al., 2020). Currently, few clinically approved repurposed antiviral drugs such as favipiravir, remdesivir, lopinavir, hydroxychloroquine (or chloroquine) and dexamethasone was targeted against SARS-CoV-2 (Jeyanthi and Kumar, 2020). In april 2020, these antiviral drugs, monoclonal antibodies, and few vaccine candidates have entered the human clinical trials. Table 1 represents the list of repurposed drugs and updates on a clinical trial. At present, few efficient antiviral agents are under clinical trial to fight the disease and the clinical aspects of those agents are explored. In the present study, we highlighted some medications to find an effective treatment for this deadly virus.
TABLE 1

Recently approved repurposed drugs for COVID-19 treatment.

Sl. NoDrugDeveloper/ companyOriginal useMolecules/Enzyme inhibitionClinical trial status
1.Danoprevir combination with RitonavirRoche Pharma, SwitzerlandHepatitis C virus (HCV)NS3/4A protease inhibitorPhase IV
2.UmifenovirJSC Pharmstandard, RussiaInfluenzaInhibits target cell membrane fusion with virus.Phase IV
3Hydroxy-chloroquineIpca Laboratories, Zydus Cadila and Wallace Pharmaceuticals, IndiaMalaria, Rheumatoid arthritis, Chronic discoid lupus erythematosus and Systemic lupus erythematosusTerminal glycosylation of ACE2Phase III/IV (Discontinued by WHO on July 2020)
4.RamdesivirGilead Sciences, United StatesEbola and Nipah virusRNA-dependent RNA polymerasePhase III/IV
5.Lopinavir/RitonavirAbbott Laboratories, United StatesHuman immunodeficiency viruses (HIV)ProteasePhase III/IV
6FavipiravirFujifilm Toyama Chemical company Limited, JapanInfluenza virusRNA-dependent RNA polymerasePhase III/IV
7.DexamethasoneZydus Cadila pharmaceutical company, IndiaRheumatic problems, asthma, skin and lung diseasesPhospholipase A2Phase III
8.OseltamivirTaj pharmaceutucals, IndiaInfluenzaNeuraminidase inhibitorPhase III
9.SarilumabRegeneron Pharmaceuticals, United States and Sanofi pharmaceutical company, FranceRheumatoid arthritisanti IL-6 receptor monoclonal antibodyPhase III
10.TocilizumabGenentech, United States and Hoffmann-La Roche, SwitzerlandRheumatoid arthritisanti IL-6 receptor monoclonal antibodyPhase III
11.LezilumabHumanigen, United StatesNew monoclonal antibody against pneumoniaanti GM-CSF receptorPhase III
Recently approved repurposed drugs for COVID-19 treatment.

Antiviral Drugs

Remdesivir

Remdesivir is a broad-spectrum antiviral drug designed by Gilead Sciences, an American biopharmaceutical company. Previously, this drug has proven effective in vitro antiviral activity against Ebola, Nipah, and Respiratory syncytial virus. Subsequently, the drug was shown to be effective against other coronaviruses such as SARS (Severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) both in vitro and in animal models (Scavone et al., 2020). The SARS CoV-2 virus replication takes place using a particular enzyme known as the RNA-dependent RNA polymerase. Researchers proved that the remdesivir could block this enzyme necessary for viral replication (Gordon et al., 2020). Remdesivir is an adenosine nucleoside analog, which incorporates into viral RNA chains, causing premature breakage by interfering with viral replication. Many clinical trials were underway assessing remdesivir as a potential treatment for COVID-19 treatment. In China, during the period of February-March 2020, a clinical trial on remdesivir showed ineffective treatment of COVID-19 patients and caused many harmful effects (Wang et al., 2020). In March 2020, scientists proved that the progression of COVID-19 was reduced in rhesus macaque monkeys after treatment with remdesivir (Williamson et al., 2020). On April 29, 2020, the United States National Institute of Allergy and Infectious Diseases (NIAID) reported that the drug provided a 31% faster recovery in 11 days. On the other hand, a double-blind, randomized, placebo-controlled trial was carried out by the United States National Institutes of Health. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by up to nine more days of 100 mg daily) or placebo for up to 10 days of treatment. The study suggested that remdesivir was found to be effective in COVID-19 patients and reduced the recovery time from 15 to 11 days. In August 2020, the FDA expanded the emergency use authorization (EUA) for the use of remdesivir in treating COVID-19 patients. Thereafter, on October 22, 2020, FDA approved and also revised the EUA to authorize the use of this drug.

Favipiravir

Favipiravir is an antiviral drug used to treat the influenza virus. The drug has also shown antiviral activities against several RNA viruses. Hence, it could be a promising agent for SARS-CoV-2 infection, which is also an RNA virus (Dong et al., 2020). Favipiravir is metabolized to its active form favipiravir-ribofuranosyl-5′-triphosphate (favipiravir-RTP), which inhibits RNA-dependent RNA polymerase (RdRp) enzyme. It interferes with the elongation of the RNA strand and prevents viral replication (Furuta et al., 2009). In China, a clinical trial on favipiravir was initiated in February 2020. The test was conducted on 80 patients by the National Clinical Research Center for Infectious Diseases. The potent antiviral action was noticed with fewer adverse effects. CT (computerized tomography) scan results revealed the eradication of the virus in 91% of people (Cai et al., 2020; Dong et al., 2020). Later, in Wuhan, the research was carried out in 240 COVID-19 patients and the scientists observed that the patients treated with favipiravir have recovered from cough and fever, but no changes were observed in patients receiving prolonged ventilation (Regalado, 2020). On March 22, 2020, Italy approved this drug for clinical trials only in the severely affected COVID-19 patients. In India, the drug was approved for treatment under the name “Fabiflu”.

Lopinavir/Ritonavir

The combination drug lopinavir/ritonavir (Kaletra) belongs to the class of protease inhibitors used for the treatment of the human immunodeficiency virus (HIV). The drug inhibits the replication of the virus by binding to the HIV protease enzyme. Some researchers have proved the efficacy of the drug against other coronaviruses such as SARS and MERS. Cao et al. (2020) conducted a trial of LopinavirRitonavir in adults Hospitalized with severe COVID-19. Their study result showed that the combinational drug was not effective for the treatment. However, the WHO included the drug in the “Global Solidarity trial” for the treatment. Currently, this drug is under clinical trial for the treatment of COVID-19 positive patients with cancer and immune suppression (National Library of Medicine (U.S.), 2020-2021c).

Hydroxychloroquine

It is generally used to treat malaria, rheumatoid arthritis, systemic lupus erythematosus, and porphyria cutanea tarda. In the malarial parasites, hydroxychloroquine accumulate in the lysosomes, increase the pH of the vacuole, inhibits the ability of parasites to proteolyze the hemoglobin and prevents the growth of the parasite (Lei et al., 2020). Likewise, in human cells, the drug increased the pH in endosomes and prevents the entry of SARS-CoV-2 virus particles. The Angiotensin-converting enzyme 2 (ACE2) enzymes are normally expressed at the outer surface of human cells. ACE2 serves as the functional receptor for the entry of SARS-CoV-2 (Venkat Kumar et al., 2020). The terminal glycosylation of ACE2 is inhibited by hydroxychloroquine, prevents the interaction of ACE2 with SARS-CoV-2spike” protein, and hence inhibits the entry of the virus. Clinical studies from China showed that the hydroxychloroquine reduced the risk of progression to severe illness in COVID-19 patients (Chen et al., 2020). In February 2020, a non-randomized study in a small sample size from France shows that the hydroxychloroquine plus azithromycin treatment reduced the viral load in COVID-19 patients (Gautret et al., 2020). Another study from France reported that the hydroxychloroquine plus azithromycin have no strong antiviral activity in severely affected COVID-19 patients (Molina et al., 2020). However, in april 2020, Hydroxychloroquine was approved by FDA for emergency use. Based on the clinical research analysis and scientific data, the FDA reported that hydroxychloroquine is ineffective in treating COVID-19 and revoked the emergency use authorization in June 2020.

Monoclonal Antibodies

Sarilumab

Sarilumab is a human monoclonal antibody generally used for the treatment of rheumatoid arthritis in adults. Zhao (2020) suggested that the sarilumab antibody could inhibit the production of a cytokine IL-6 in the patients with COVID-19 pneumonia. A randomized, double-blind, placebo-controlled, phase three trial of sarilumab in patients admitted to Hospital with severe or critical COVID-19 was studied. Their result shows that the sarilumab efficacy is poor in patients admitted to Hospital with COVID-19 and receiving supplemental oxygen (Lescure et al., 2021).

Tocilizumab

Tocilizumab is another monoclonal antibody against IL-6 used for the treatment of rheumatoid arthritis and systemic juvenile idiopathic arthritis in children. The drug could prevent the expression of IL-6 in COVID-19 patients (Luo et al., 2020). In March 2021, FDA approved this tocilizumab for clinical trials to evaluate its safety and efficiency (National Library of Medicine, 2021). But, the scientific evidence showed that a randomized double-blind clinical trial was not effective to prevent death in severely affected COVID-19 patients.

Lenzilumab

Lenzilumab is a monoclonal antibody used for the treatment of chronic and juvenile myelomonocytic leukemia. Lenzilumab is used to block the expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF). The COVID-19 Hospitalized patients have higher levels of the inflammatory cytokine GM-CSF in the plasma, which is reported to be a key to trigger the disease (Huang et al., 2020). In May 2020, FDA has approved lenzilumab to enter the clinical trial (National Library of Medicine (U.S.), 2020-2021b).

Vaccines

Over the past century, numerous successful attempts have been made to develop vaccines for polio, cholera, measles, typhoid, and tetanus. Apart from attenuated vaccines, conjugate and subunit vaccines are also proved to be efficient against pneumonia, sepsis, and meningitis (Kim et al., 2020). Currently, more than 150 vaccine candidates for SARS-CoV-2 are under development at various stages. There has been an increased focus on the pre-clinical development of COVID-19 vaccines by many research institutes and vaccine manufacturers around the world. Currently, the predominant vaccine platforms for pre-clinical studies included are DNA, RNA, inactivated virus, viral vector (Replicating and Non-Replicating), live attenuated virus, protein subunit and virus-like particle (VLP) (Bezbaruah et al., 2021; Borah et al., 2021). Though many vaccines have been included in clinical trials, vaccine candidates such as AZD1222 (Covishield, Vaxzevria), BNT162b2 mRNA-1273 and CoronaVac are in the phase IV clinical trial (Table 2). Currently (as of May 11, 2021), over 99 vaccine candidates are under assessment in clinical trials on humans and 184 under pre-clinical trials on animals (WHO, 2020). Recently, regulatory authorities in some countries have authorized mRNA vaccines, recombinant adenoviral vectors vaccines, and commonly used inactivated virus vaccines for emergency use. So far, globally, there have been 30 active vaccine projects that involve the development of mRNA vaccines, recombinant adenoviral vectors vaccines, and inactivated virus vaccines. Despite the number of vaccine development projects, WHO has so far validated only six vaccines globally, the Pfizer-BioNTech vaccine, the Johnson and Johnson vaccine, Sputnik V, Sinopharm-BIBP, Moderna and two AstraZeneca vaccines (produced by SKBio in the Republic of Korea and Serum Institute of India) for emergency use. These vaccines are proved to be safe and effective by the WHO Strategic Advisory Group of Experts on Immunization (Acharya et al., 2021). The Pfizer-BioNTech vaccine is a mRNA type vaccine that can be delivered intramuscular with two dose series separated by a 21 days interval. Based on the published evidence from clinical trials, the Pfizer-BioNTech vaccine is reported to be 95% effective at preventing laboratory-confirmed COVID-19 illness in people without the history of previous infection (Centers for Disease Control and Prevention, 2021b). The Johnson and Johnson vaccine is however a viral vector type which can be delivered intramuscular with a single dose. Based on the clinical trial publication evidences, the Johnson and Johnson vaccine is reported to be 66.3% effective after 2 weeks of vaccination at preventing laboratory-confirmed COVID-19 illness in people who had no history of prior infection (Centers for Disease Control and Prevention, 2021a). Particularly, AstraZeneca vaccine is co-invented by the University of Oxford and its spin-out company, Vaccitech. It is a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees and contains the genetic material of the SARS-CoV-2 virus spike protein. The vaccine is delivered intramuscular with a two dose series that are separated by 4 weeks. The AstraZeneca vaccine phase III clinical trial data is reported to be 79% effective at preventing symptomatic COVID-19 and 100% efficacy at preventing severe disease and Hospitalization (National Library of Medicine (U.S.), 2020-2021a). The Moderna COVID-19 vaccine is developed by Moderna, the United States National Institute of Allergy and Infectious Diseases (NIAID) and the Biomedical Advanced Research and Development Authority (BARDA). It is a mRNA-1273 vaccine encapsulated with lipid nanoparticles, delivered intramuscular with a two dose series separated by 28 days. The phase III clinical trial reported to be 94.1% efficacy at preventing COVID-19 illness, including severe disease (Baden et al., 2021). Sinopharm BIBP is a COVID-19 vaccine produced by the China National Pharmaceutical Group (Sinopharm) and its Beijing Institute of Biological Products (BIBP). It is an inactivated virus vaccine, delivered intramuscular with a two dose series separated by 21 days. The phase III clinical trial reported to be 79% efficacy against COVID-19 symptomatic and Hospitalized patients (WHO, 2021). Covaxin is India’s first vaccine, developed by Bharat Biotech Company in collaboration with the Indian Council of Medical Research (ICMR) and National Institute of Virology (NIV). The vaccine is an inactivated SARS-CoV-2 virus, delivered intramuscular with a two dose series separated by 28 days. Covaxin phase III clinical trial data is reported to be 81% interim efficacy in preventing COVID-19 illness in people without prior infection after the second dose (National Library of Medicine (U.S.), 2020-2021d). Russia’s first approved COVID-19 vaccine is Sputnik V. It is an adenoviral DNA-based vaccine. The phase III trial of Sputnik V is reported to be 91.6% efficacy against COVID-19 illness patients (Jones and Roy, 2021). The vaccines currently in clinical trials are summarized in Table 2. The cold storage of vaccines is crucial to reduce the loss of stability, and immunogenicity. The two promising COVID-19 mRNA vaccines, including BioNTech/Pfizer and Moderna are to be stored in ultra-cold storage conditions at −70°C and −18°C, respectively. These vaccines are encapsulated in lipid nanoparticles (LNPs) which have the advantage of delivering the mRNA by protecting them from enzyme degradation and it can effectively deliver mRNA vaccines into the cell cytosol through a series of endocytosis mechanisms. (Acharya et al., 2021; Baden et al., 2021). The ultra-cold storage of the BioNTech/Pfizer vaccine would be unsuitable for low and middle-income countries due to a shortage of cold-chain infrastructure. The maintenance of mRNA-LNPs in a frozen form will be a major challenge for transport, storage, and distribution in developing countries, resulting in reduced immunization rates. On the other hand, AstraZeneca’s vaccine can be stored, transported, and handled at normal refrigerated conditions (2–8 °C) for at least six months. Moreover, comparing to the other types of vaccine, the cost of the AstraZeneca’s vaccine is very less (around $2-4 per dose). Hence, it can be easily produced for a larger population and distributed using existing medical facilities in developing countries.
TABLE 2

Vaccine candidates under investigation in the clinical trial of COVID-19.

Sl. NoVaccine candidateDescription/typeManufacturer/Institution and locationTrial phase
1AZD1222 (Covishield, Vaxzevria)adenoviral vectorAstraZeneca, University of Oxford and SK bioscience South KoreaPhase IV
2CoronaVacInactivated or killed SARS-CoV-2Sinovac Biotech, ChinaPhase IV
3BNT162b2RNAPfizer, United States, BioNTech, Germany and Fosun Pharma, China andPhase IV
4mRNA-1273Lipid nanoparticle assisted mRNA deliveryModerna and United States National Institute of Allergy and Infectious Diseases, United StatesPhase IV
5Ad5-nCoVRecombinant adenoviral vectorCanSino Biologics, ChinaPhase III
6NVX-CoV2373SARS-CoV-2 recombinant spike protein nanoparticlesNovavax, AustraliaPhase III
7BBIBP-CorV (Sinopharm)Inactivated SARS-CoV-2Beijing Institute of Biological Products, ChinaPhase III
8Minhai COVID-19 vaccineInactivated SARS-CoV-2Minhai Biotechnology Co., ChinaPhase III
9Sputnik VAdenoviral vectorGamaleya Research Institute, RussiaPhase III
10Ad26.COV2.SAdenoviral vectorJanssen Pharmaceutical Companies, BelgiumPhase III
11InactivatedInactivated SARS-CoV-2Chinese Academy of Medical Sciences, ChinaPhase III
12ZF2001 (RBD-Dimer)Protein SubunitAnhui Zhifei Longcom Biopharmaceutical/Institute of Microbiology, Chinese Academy of Sciences, ChinaPhase III
13CVnCoVRNACurevac, biopharmaceutical company, GermanyPhase III
14CoviVacInactivated SARS-CoV-2Chumakov Center, Russian Academy of SciencesPhase III
15CIGB-66 (ABDALA)Protein subunitCenter for Genetic Engineering and Biotechnology, CubaPhase III
16ZyCoV-DDNAZydus Cadila, IndiaPhase III
17BBV152 (Covaxin)Inactivated SARS-CoV-2Bharat Biotech, IndiaPhase III
18EpiVacCoronaPeptide subunitState Research Center of Virology and Biotechnology VECTOR, RussiaPhase III
19GRAd-COV2Adenovirus vectorLazzaro Spallanzani National Institute for Infectious Diseases, ItalyPhase II/III
20COVIran BarakatInactivated SARS-CoV-2Barakat Pharmaceutical Group, IranPhase II/III
21INO-4800Electroporation delivered DNA vaccinesInovio Pharmaceuticals, United States and International Vaccine Institute, South KoreaPhase II/III
22AG0302-COVID-19DNA Vaccine (plasmid)Osaka University/ AnGes/ Takara Bio Inc., JapanPhase II/III
23SCB-2019Protein SubunitClover Biopharmaceuticals, chinaPhase II/III
24UB-612Protein SubunitUnited Biomedical Inc., United States and DASA, BrazilPhase II/III
25CoVLPVirus like particlesMedicago Inc., CanadaPhase II/III
26MVC-COV1901Protein SubunitMedigen Vaccine Biologics Corporation, TaiwanPhase II
27NanocovaxSARS-CoV-2 recombinant spike protein subunitNanogen Pharmaceutical Biotechnology JSC, VietnamPhase II
28ERUCOV-VACInactivated SARS-CoV-2Health Institutes of TurkeyPhase II
29DelNS1-2019-nCoV-RBD-OPTReplicating Viral VectorBeijing Wantai Biological Pharmacy, ChinaPhase II
30ARCT-021RNAArcturus Therapeutics, United states and Duke–NUS Medical School, SingaporePhase II
31LV-SMENP-DCDendritic cells modified with lentiviral vectorShenzhen Geno-Immune Medical Institute, ChinaPhase I/II
32GX-19DNA VaccineGenexine Consortium, South KoreaPhase I/II
33KBP-201 (RBD-based)Protein SubunitKentucky Bioprocessing, Inc., United StatesPhase I/II
34IIBR-100 (Brilife)Vesicular stomatitis vector (recombinant)Israel Institute for Biological ResearchPhase I/II
35RBD SARS-CoV-2 HBsAg VLPsVirus-like particleSerum Institute of India Accelagen Pty, Australia and SpyBiotech, United kingdomPhase I/II
36GBP510Protein subunitSK Bioscience Co., Ltd. London and CEPI, NorwayPhase I/II
37VBI-2902Virus-like particleVariation Biotechnologies, United StatesPhase I/II
38NDV-HXP-SViral vectorMahidol University, ThailandPhase I/II
39EuCorVac-19Protein subunitEuBiologics Co, South KoreaPhase I/II
40AV-COVID-19Viral vectorAIVITA Biomedical, Inc., United States and Ministry of Health, IndonesiaPhase I/II
41COVID-eVaxDNATakis Biotech, ItalyPhase I/II
42ChulaCov19RNAChulalongkorn University, ThailandPhase I/II
43Bio E COVID-19 (BECOV2D)Subunit (antigen)Biological E. Limited, India and Baylor College of Medicine, United StatesPhase I/II
44Covigenix VAX-001DNAEntos Pharmaceuticals Inc., CanadaPhase I
45bacTRL-SpikeDNASymvivo Corporation, (biotechnology company) CanadaPhase I
46Covid-19/aAPCLentiviral vectorShenzhen Geno-Immune Medical Institute, ChinaPhase I
47MVA-SARS-2-SNon-Replicating Viral VectorUniversity of Munich (Ludwig-Maximilians), GermanyPhase I
48COVAX-19Protein SubunitVaxine Pty Ltd/Medytox, AustraliaPhase I
49.Molecular clamp stabilized Spike protein with MF59 adjuvantProtein SubunitUniversity of Queensland/CSL Ltd., AustraliaPhase I
50CoVac-1Protein SubunitUniversity Hospital Tuebingen, GermanyPhase I
51COVI-VACAttenuatedCodagenix Inc., United states and Serum institute of IndiaPhase I
52PTX-COVID19-BRNAProvidence Therapeutics, CanadaPhase I
53COVIGENDNAUniversity of Sydney, AustraliaPhase I
54BBV154Adenovirus vectorBharat Biotech, IndiaPhase I
55NBP2001DNASK Bioscience Co. Ltd., South KoreaPhase I
56DelNS1-nCoV-RBD LAIVAttenuatedUniversity of Hong KongPhase I
57LNP-nCoVsaRNARNAImperial College LondonPhase I
58ChulaCov19 mRNA vaccineRNAChulalongkorn University, ThailandPhase I
59AdCOVIDNon-replicating Viral vectorAltimmune, Inc., United StatesPhase I
60mRNA-1283RNAModerna Inc., United StatesPhase I

Source: https:// www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate vaccines.

Vaccine candidates under investigation in the clinical trial of COVID-19. Source: https:// www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate vaccines.

Conclusion

In the present study, the possible therapeutic options described are solely based on the latest research findings for the treatment of COVID 19. We have summarized the current status of the repurposing drugs, including remdesivir, favipiravir, lopinvar/retinovar, hydroxychloroquine, monoclonal antibodies and vaccines against the SARS-CoV-2 infection. The development of new drugs is a complex and prolonged process. Hence, repurposed drugs could be an alternative to combat COVID-19. However, vaccines under clinical trials are showing great results compared to the other therapeutics options. More than 100 vaccines are under study, among that only four vaccines have been approved by WHO for the prevention and treatment of COVID-19. The WHO encourages COVID-19 vaccine manufacturers in many countries and ensures its safety in immunization. The vaccines were found to be safe for adults, including those with pre-existing auto-immune disorders. Several vaccines have received emergency use authorization in many countries but careful monitoring in high-risk individuals over the age of 60 is still required.
  25 in total

Review 1.  Vaccines and drugs under clinical trials for prevention and treatment of COVID-19.

Authors:  Umesh C S Yadav
Journal:  Virusdisease       Date:  2021-03-22

2.  Discovering drugs to treat coronavirus disease 2019 (COVID-19).

Authors:  Liying Dong; Shasha Hu; Jianjun Gao
Journal:  Drug Discov Ther       Date:  2020

Review 3.  Current pharmacological treatments for COVID-19: What's next?

Authors:  Cristina Scavone; Simona Brusco; Michele Bertini; Liberata Sportiello; Concetta Rafaniello; Alice Zoccoli; Liberato Berrino; Giorgio Racagni; Francesco Rossi; Annalisa Capuano
Journal:  Br J Pharmacol       Date:  2020-05-15       Impact factor: 8.739

4.  Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial.

Authors:  Yeming Wang; Dingyu Zhang; Guanhua Du; Ronghui Du; Jianping Zhao; Yang Jin; Shouzhi Fu; Ling Gao; Zhenshun Cheng; Qiaofa Lu; Yi Hu; Guangwei Luo; Ke Wang; Yang Lu; Huadong Li; Shuzhen Wang; Shunan Ruan; Chengqing Yang; Chunlin Mei; Yi Wang; Dan Ding; Feng Wu; Xin Tang; Xianzhi Ye; Yingchun Ye; Bing Liu; Jie Yang; Wen Yin; Aili Wang; Guohui Fan; Fei Zhou; Zhibo Liu; Xiaoying Gu; Jiuyang Xu; Lianhan Shang; Yi Zhang; Lianjun Cao; Tingting Guo; Yan Wan; Hong Qin; Yushen Jiang; Thomas Jaki; Frederick G Hayden; Peter W Horby; Bin Cao; Chen Wang
Journal:  Lancet       Date:  2020-04-29       Impact factor: 79.321

5.  Cytokine storm and immunomodulatory therapy in COVID-19: Role of chloroquine and anti-IL-6 monoclonal antibodies.

Authors:  Ming Zhao
Journal:  Int J Antimicrob Agents       Date:  2020-04-16       Impact factor: 5.283

6.  Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine.

Authors:  Lindsey R Baden; Hana M El Sahly; Brandon Essink; Karen Kotloff; Sharon Frey; Rick Novak; David Diemert; Stephen A Spector; Nadine Rouphael; C Buddy Creech; John McGettigan; Shishir Khetan; Nathan Segall; Joel Solis; Adam Brosz; Carlos Fierro; Howard Schwartz; Kathleen Neuzil; Larry Corey; Peter Gilbert; Holly Janes; Dean Follmann; Mary Marovich; John Mascola; Laura Polakowski; Julie Ledgerwood; Barney S Graham; Hamilton Bennett; Rolando Pajon; Conor Knightly; Brett Leav; Weiping Deng; Honghong Zhou; Shu Han; Melanie Ivarsson; Jacqueline Miller; Tal Zaks
Journal:  N Engl J Med       Date:  2020-12-30       Impact factor: 91.245

7.  [A pilot study of hydroxychloroquine in treatment of patients with moderate COVID-19].

Authors:  Jun Chen; Danping Liu; Li Liu; Ping Liu; Qingnian Xu; Lu Xia; Yun Ling; Dan Huang; Shuli Song; Dandan Zhang; Zhiping Qian; Tao Li; Yinzhong Shen; Hongzhou Lu
Journal:  Zhejiang Da Xue Xue Bao Yi Xue Ban       Date:  2020-05-25

8.  A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19.

Authors:  Bin Cao; Yeming Wang; Danning Wen; Wen Liu; Jingli Wang; Guohui Fan; Lianguo Ruan; Bin Song; Yanping Cai; Ming Wei; Xingwang Li; Jiaan Xia; Nanshan Chen; Jie Xiang; Ting Yu; Tao Bai; Xuelei Xie; Li Zhang; Caihong Li; Ye Yuan; Hua Chen; Huadong Li; Hanping Huang; Shengjing Tu; Fengyun Gong; Ying Liu; Yuan Wei; Chongya Dong; Fei Zhou; Xiaoying Gu; Jiuyang Xu; Zhibo Liu; Yi Zhang; Hui Li; Lianhan Shang; Ke Wang; Kunxia Li; Xia Zhou; Xuan Dong; Zhaohui Qu; Sixia Lu; Xujuan Hu; Shunan Ruan; Shanshan Luo; Jing Wu; Lu Peng; Fang Cheng; Lihong Pan; Jun Zou; Chunmin Jia; Juan Wang; Xia Liu; Shuzhen Wang; Xudong Wu; Qin Ge; Jing He; Haiyan Zhan; Fang Qiu; Li Guo; Chaolin Huang; Thomas Jaki; Frederick G Hayden; Peter W Horby; Dingyu Zhang; Chen Wang
Journal:  N Engl J Med       Date:  2020-03-18       Impact factor: 91.245

9.  COVID-19 vaccines: breaking record times to first-in-human trials.

Authors:  Young Chan Kim; Barbara Dema; Arturo Reyes-Sandoval
Journal:  NPJ Vaccines       Date:  2020-04-30       Impact factor: 7.344

Review 10.  Developmental Landscape of Potential Vaccine Candidates Based on Viral Vector for Prophylaxis of COVID-19.

Authors:  Rajashri Bezbaruah; Pobitra Borah; Bibhuti Bhushan Kakoti; Nizar A Al-Shar'I; Balakumar Chandrasekaran; Da'san M M Jaradat; Munir A Al-Zeer; Saeid Abu-Romman
Journal:  Front Mol Biosci       Date:  2021-04-15
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Journal:  Elife       Date:  2022-03-24       Impact factor: 8.140

Review 2.  Advances in the development of therapeutic strategies against COVID-19 and perspectives in the drug design for emerging SARS-CoV-2 variants.

Authors:  Jialing Yin; Chengcheng Li; Chunhong Ye; Zhihui Ruan; Yicong Liang; Yongkui Li; Jianguo Wu; Zhen Luo
Journal:  Comput Struct Biotechnol J       Date:  2022-01-31       Impact factor: 7.271

3.  Case of possible encephalopathy following receiving the first dose of Iranian COVID-19Vaccine; COVIran Barakat.

Authors:  Mohammad Javad Fallahi; Navid Esmaeilzadeh Shahri; Zohre Khodamoradi; Moazameh Meymandi Nia; Faezeh Sehatpour; Laleh Mahmoudi
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