Current status of therapeutic approaches and vaccines for SARS-CoV-2

SARS-CoV-2, declared a pandemic in March 2020, is the current global health challenge. The global bioburden of this virus is increasing at a rapid pace. Many antiviral drugs and vaccines have been registered for clinical trials because of their inhibitory activity observed in vitro. Currently, five types of vaccines have successfully passed Phase IV clinical trial and are being administered in populations worldwide. A plethora of experimental designs have been proposed worldwide in order to find a safe and efficacious treatment option. Therefore, it is necessary to provide baseline data and information to clinicians and researchers so that they can review the current status of therapeutics and efficacy of already developed vaccines. This review article summarizes all therapeutic options that may help to combat SARS-CoV-2.

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Current Status of HIV-1 Vaccines

Vaccines ◽

10.3390/vaccines9091026 ◽

2021 ◽

Vol 9 (9) ◽

pp. 1026

Author(s):

Anna Hargrave ◽

Abu Salim Mustafa ◽

Asma Hanif ◽

Javed H. Tunio ◽

Shumaila Nida M. Hanif

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Global Health ◽

Low Income ◽

Vaccine Development ◽

Low Income Countries ◽

Current Status ◽

Health Challenge ◽

Hiv 1 ◽

Global Health Challenge

HIV-1 infection and its progression to AIDS remains a significant global health challenge, particularly for low-income countries. Developing a vaccine to prevent HIV-1 infections has proven to be immensely challenging with complex biological acquisition and infection, unforeseen clinical trial disappointments, and funding issues. This paper discusses important landmarks of progress in HIV-1 vaccine development, various vaccine strategies, and clinical trials.

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Nature-derived hit, lead, and drug-like small molecules: Current status and future aspects against key target proteins of Coronaviruses

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557521666210805113231 ◽

2021 ◽

Vol 21 ◽

Author(s):

Md. Junaid ◽

Yeasmin Akter ◽

Aysha Siddika ◽

S. M. Abdul Nayeem ◽

Afsana Nahrin ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Small Molecules ◽

Current Status ◽

Future Research ◽

Literature Study ◽

Lead Compounds ◽

Human Coronaviruses

Background: COVID-19 pandemic, the most unprecedented event of the year 2020, has brought millions of scientists worldwide in a single platform to fight against it. Though several drugs are now in the clinical trial, few vaccines available on the market already but the lack of an effect of those is making the situation worse. Aim of the study: In this review, we demonstrated comprehensive data of natural antiviral products showing activities against different proteins of Human Coronaviruses (HCoV) that are responsible for its pathogenesis. Furthermore, we categorized the compounds into the hit, lead, and drug based on the IC50/EC50 value, drug-likeness, and lead-likeness test to portray their potentiality to be a drug. We also demonstrated the present status of our screened antiviral compounds with respect to clinical trials and reported the lead compounds that can be promoted to clinical trial against COVID-19. Methods: A systematic search strategy was employed focusing on Natural Products (NPs) with proven activity (in vitro, in vivo, or in silico) against human coronaviruses, in general, and data were gathered from databases like PubMed, Web of Science, Google Scholar, SciVerse, and Scopus. Information regarding clinical trials retrieved from the Clinical Trial database. Results: Total "245" natural compounds were identified initially from the literature study. Among them, Glycyrrhizin, Caffeic acid, Curcumin is in phase 3, and Tetrandrine, Cyclosporine, Tacrolimus, Everolimus are in phase 4 clinical trial. Except for Glycyrrhizin, all compounds showed activity against COVID-19. Conclusions: In summary, our demonstrated specific small molecules with lead and drug-like capabilities clarified their position in the drug discovery pipeline and proposed their future research against COVID-19.

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Therapeutic Effectiveness and Safety of Repurposing Drugs for the Treatment of COVID-19: Position Standing in 2021

Frontiers in Pharmacology ◽

10.3389/fphar.2021.659577 ◽

2021 ◽

Vol 12 ◽

Author(s):

Safaet Alam ◽

Taslima Binte Kamal ◽

Md. Moklesur Rahman Sarker ◽

Jin-Rong Zhou ◽

S. M. Abdur Rahman ◽

...

Keyword(s):

Clinical Trials ◽

Case Series ◽

Basic Knowledge ◽

World Health ◽

Current Status ◽

Drug Candidates ◽

Health Organization ◽

Meta Analyses

COVID-19, transmitted by SARS-CoV-2, is one of the most serious pandemic situations in the history of mankind, and has already infected a huge population across the globe. This horrendously contagious viral outbreak was first identified in China and within a very short time it affected the world's health, transport, economic, and academic sectors. Despite the recent approval of a few anti-COVID-19 vaccines, their unavailability and insufficiency along with the lack of other potential therapeutic options are continuing to worsen the situation, with valuable lives continuing to be lost. In this situation, researchers across the globe are focusing on repurposing prospective drugs and prophylaxis such as favipiravir, remdesivir, chloroquine, hydroxychloroquine, ivermectin, lopinavir-ritonavir, azithromycin, doxycycline, ACEIs/ARBs, rivaroxaban, and protease inhibitors, which were preliminarily based on in vitro and in vivo pharmacological and toxicological study reports followed by clinical applications. Based on available preliminary data derived from limited clinical trials, the US National Institute of Health (NIH) and USFDA also recommended a few drugs to be repurposed i.e., hydroxychloroquine, remdesivir, and favipiravir. However, World Health Organization later recommended against the use of chloroquine, hydroxychloroquine, remdesivir, and lopinavir/ritonavir in the treatment of COVID-19 infections. Combining basic knowledge of viral pathogenesis and pharmacodynamics of drug molecules as well as in silico approaches, many drug candidates have been investigated in clinical trials, some of which have been proven to be partially effective against COVID-19, and many of the other drugs are currently under extensive screening. The repurposing of prospective drug candidates from different stages of evaluation can be a handy wellspring in COVID-19 management and treatment along with approved anti-COVID-19 vaccines. This review article combined the information from completed clinical trials, case series, cohort studies, meta-analyses, and retrospective studies to focus on the current status of repurposing drugs in 2021.

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Implementing Curcumin in Translational Oncology Research

Molecules ◽

10.3390/molecules25225240 ◽

2020 ◽

Vol 25 (22) ◽

pp. 5240

Author(s):

Koraljka Gall Trošelj ◽

Ivana Samaržija ◽

Marko Tomljanović ◽

Renata Novak Kujundžić ◽

Nikola Đaković ◽

...

Keyword(s):

Clinical Trials ◽

Clinical Studies ◽

Metabolic Reprogramming ◽

Current Status ◽

Strong Indication ◽

Experimental Animals ◽

Oncology Research ◽

Modifying Effect ◽

Detailed Presentation

Most data published on curcumin and curcumin-based formulations are very promising. In cancer research, the majority of data has been obtained in vitro. Less frequently, researchers used experimental animals. The results of several clinical studies are conclusive, and these studies have established a good foundation for further research focusing on implementing curcumin in clinical oncology. However, the issues regarding timely data reporting and lack of disclosure of the exact curcumin formulations used in these studies should not be neglected. This article is a snapshot of the current status of publicly available data on curcumin clinical trials and a detailed presentation of results obtained so far with some curcumin formulations. Phenomena related to the observed effects of curcumin shown in clinical trials are presented, and its modifying effect on gut microbiota and metabolic reprogramming is discussed. Based on available data, there is a strong indication that curcumin and its metabolites present molecules that do not necessarily need to be abundant in order to act locally and benefit systemically. Future clinical studies should be designed in a way that will take that fact into consideration.

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Polymer–drug conjugates: towards a novel approach for the treatment of endrocine-related cancer

Endocrine Related Cancer ◽

10.1677/erc.1.01045 ◽

2005 ◽

Vol 12 (Supplement_1) ◽

pp. S189-S199 ◽

Cited By ~ 117

Author(s):

R Duncan ◽

M J Vicent ◽

F Greco ◽

R I Nicholson

Keyword(s):

Clinical Trials ◽

Anticancer Agents ◽

Antitumour Activity ◽

Metastatic Cancer ◽

Clinical Results ◽

Water Soluble ◽

Current Status ◽

Hpma Copolymer ◽

Drug Conjugates

The last decade has seen successful clinical application of polymer–protein conjugates (e.g. Oncaspar, Neulasta) and promising results in clinical trials with polymer–anticancer drug conjugates. This, together with the realisation that nanomedicines may play an important future role in cancer diagnosis and treatment, has increased interest in this emerging field. More than 10 anticancer conjugates have now entered clinical development. Phase I/II clinical trials involving N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-doxorubicin (PK1; FCE28068) showed a four- to fivefold reduction in anthracycline-related toxicity, and, despite cumulative doses up to 1680 mg/m2 (doxorubicin equivalent), no cardiotoxicity was observed. Antitumour activity in chemotherapy-resistant/refractory patients (including breast cancer) was also seen at doxorubicin doses of 80–320 mg/m2, consistent with tumour targeting by the enhanced permeability (EPR) effect. Hints, preclinical and clinical, that polymer anthracycline conjugation can bypass multidrug resistance (MDR) reinforce our hope that polymer drugs will prove useful in improving treatment of endocrine-related cancers. These promising early clinical results open the possibility of using the water-soluble polymers as platforms for delivery of a cocktail of pendant drugs. In particular, we have recently described the first conjugates to combine endocrine therapy and chemotherapy. Their markedly enhanced in vitro activity encourages further development of such novel, polymer-based combination therapies. This review briefly describes the current status of polymer therapeutics as anticancer agents, and discusses the opportunities for design of second-generation, polymer-based combination therapy, including the cocktail of agents that will be needed to treat resistant metastatic cancer.

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Molnupiravir: a novel efficacious antiviral candidate to COVID-19

Research Society and Development ◽

10.33448/rsd-v10i15.23014 ◽

2021 ◽

Vol 10 (15) ◽

pp. e281101423014

Author(s):

I Wayan Sumardika ◽

Cokorda Agung Wahyu Purnamasidhi ◽

Agus Eka Darwinata ◽

Giovanca Verentzia Purnama ◽

Jerry Jerry ◽

...

Keyword(s):

Clinical Trial ◽

Human Body ◽

Rna Viruses ◽

Review Article ◽

World Health ◽

Nucleotide Analog ◽

Efficacious Treatment ◽

The World ◽

Health Organization ◽

Trial Phase

An unknown pneumonia-like disease has emerged in Wuhan, China, in late 2019. It is later named as SARS-CoV-2 which cause COVID-19. This virus spreads easily due to high mobilization and its transmission through droplets or aerosol and fomite. The World Health Organization (WHO) then declared this disease as a global outbreak in March 2020. As the world faces the outbreak of SARS-CoV-2, many researchers race to find the most efficacious treatment for COVID-19. Until now, the most common treatments for COVID-19 were only symptomatic such as decongestant, corticosteroid, interleukin inhibitor, and existing antiviral. The researchers then develop a brand new antiviral that works efficiently to inhibit SARS-CoV-2 and might become prophylaxis. This disease is called Molnupiravir or EIDD-2801, a nucleotide analog which inhibits SARS-CoV-2 replication, resulting in damaged mRNA and lethal virions. Molnupiravir works to produce mutagenesis in RNA viruses and prevent the virus from spreading widely throughout the human body. However, this drug is still needed to undergo clinical trial phase three. In this article, we will discuss how Molnupiravir works and its efficacy compared to existing drugs. This review article aims to provide an update about novel efficacious antiviral for COVID-19, Molnupiravir.

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Emerging Therapeutic Approaches to Combat COVID-19: Present Status and Future Perspectives

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.604447 ◽

2021 ◽

Vol 8 ◽

Author(s):

Karthik Vivekanandhan ◽

Poornima Shanmugam ◽

Hamed Barabadi ◽

Vigneshwaran Arumugam ◽

Dharun Daniel Raj Daniel Paul Raj ◽

...

Keyword(s):

Clinical Trials ◽

Scale Up ◽

Rapid Expansion ◽

Future Perspectives ◽

Therapeutic Approaches ◽

Vaccine Candidates ◽

Drug Candidates ◽

Life Saving ◽

Immunization Services

Coronavirus disease (COVID-19) has emerged as a fast-paced epidemic in late 2019 which is disrupting life-saving immunization services. SARS-CoV-2 is a highly transmissible virus and an infectious disease that has caused fear among people across the world. The worldwide emergence and rapid expansion of SARS-CoV-2 emphasizes the need for exploring innovative therapeutic approaches to combat SARS-CoV-2. The efficacy of some antiviral drugs such as remdesivir, favipiravir, umifenovir, etc., are still tested against SARS-CoV-2. Additionally, there is a large global effort to develop vaccines for the protection against COVID-19. Because vaccines seem the best solution to control the pandemic but time is required for its development, pre-clinical/clinical trials, approval from FDA and scale-up. The nano-based approach is another promising approach to combat COVID-19 owing to unique physicochemical properties of nanomaterials. Peptide based vaccines emerged as promising vaccine candidates for SARS-CoV-2. The study emphasizes the current therapeutic approaches against SARS-CoV-2 and some of the potential candidates for SARS-CoV-2 treatment which are still under clinical studies for their effectiveness against SARS-CoV-2. Overall, it is of high importance to mention that clinical trials are necessary for confirming promising drug candidates and effective vaccines and the safety profile of the new components must be evaluated before translation of in vitro studies for implementation in clinical use.

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Missing clinical trial data: the evidence gap in the safety of potential COVID-19 drugs

10.21203/rs.3.rs-70754/v1 ◽

2020 ◽

Author(s):

Florence Rodgers ◽

Toby Pepperrell ◽

Sarai Keestra ◽

Victoria Pilkington

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Severe Disease ◽

Safety Information ◽

Safety Data ◽

Clinical Trial Data ◽

Clinical Findings ◽

Rapid Review ◽

Clinical Trial Results

Abstract Background: Several drugs are being repurposed for the treatment of the coronavirus disease 2019 (COVID-19) pandemic based on in vitro or early clinical findings. As these drugs are being used in varied regimens and dosages, it is important to enable synthesis of existing safety data from clinical trials. However, availability of safety information is limited by a lack of timely reporting of clinical trial results on public registries or through academic publication. We aimed to analyse the evidence gap in safety data by quantifying the number of missing clinical trial results for drugs potentially being repurposed for COVID-19 by conducting a rapid review of results posting on ClinicalTrials.gov and in academic publications. Methods: ClinicalTrials.gov was searched for 19 drugs that have been identified as potential treatments for COVID-19. Relevant clinical trials for any prior indication were listed by identifier (NCT number) and checked for results and for timely result reporting (within 395 days of the primary completion date). Additionally, PubMed and Google Scholar were searched to identify publications of results not listed on the registry. A second, blinded search of 10% of trials was conducted to assess reviewer concordance. Results: Of 3754 completed trials, 1516 (40.4%) did not post results on ClinicalTrials.gov or in the academic literature. 1172 (31.2%) completed trials had tabular results on ClinicalTrials.gov. A further 1066 (28.4%) completed trials had results from the literature search, but did not report results on ClinicalTrials.gov. Key drugs missing clinical trial results include hydroxychloroquine (37.0% completed trials unreported), favipiravir (77.8%) and lopinavir (40.5%). Conclusions: There is an important evidence gap for the safety of drugs being repurposed for COVID-19. This uncertainty could cause a large burden of additional morbidity and mortality during the pandemic. We recommend caution in experimental drug use for non-severe disease and urge clinical trial sponsors to report missing results retrospectively.

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Plant-Based COVID-19 Vaccines: Current Status, Design, and Development Strategies of Candidate Vaccines

Vaccines ◽

10.3390/vaccines9090992 ◽

2021 ◽

Vol 9 (9) ◽

pp. 992

Author(s):

Puna Maya Maharjan ◽

Sunghwa Choe

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Vaccine Development ◽

Production Systems ◽

Transmission Rate ◽

Neutralizing Antibody ◽

Current Status ◽

Economic Losses ◽

Phase 2 Clinical Trial ◽

Clinical Trial Results

The prevalence of the coronavirus disease 2019 (COVID-19) pandemic in its second year has led to massive global human and economic losses. The high transmission rate and the emergence of diverse SARS-CoV-2 variants demand rapid and effective approaches to preventing the spread, diagnosing on time, and treating affected people. Several COVID-19 vaccines are being developed using different production systems, including plants, which promises the production of cheap, safe, stable, and effective vaccines. The potential of a plant-based system for rapid production at a commercial scale and for a quick response to an infectious disease outbreak has been demonstrated by the marketing of carrot-cell-produced taliglucerase alfa (Elelyso) for Gaucher disease and tobacco-produced monoclonal antibodies (ZMapp) for the 2014 Ebola outbreak. Currently, two plant-based COVID-19 vaccine candidates, coronavirus virus-like particle (CoVLP) and Kentucky Bioprocessing (KBP)-201, are in clinical trials, and many more are in the preclinical stage. Interim phase 2 clinical trial results have revealed the high safety and efficacy of the CoVLP vaccine, with 10 times more neutralizing antibody responses compared to those present in a convalescent patient’s plasma. The clinical trial of the CoVLP vaccine could be concluded by the end of 2021, and the vaccine could be available for public immunization thereafter. This review encapsulates the efforts made in plant-based COVID-19 vaccine development, the strategies and technologies implemented, and the progress accomplished in clinical trials and preclinical studies so far.

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LSD1 as a Biomarker and the Outcome of Its Inhibitors in the Clinical Trial: The Therapy Opportunity in Tumor

Journal of Oncology ◽

10.1155/2021/5512524 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Clement Agboyibor ◽

Jianshu Dong ◽

Clement Yaw Effah ◽

Emmanuel Kwateng Drokow ◽

Waqar Pervaiz ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Clinical Results ◽

Tumor Patients ◽

Therapy Targets ◽

Dosing Regimens ◽

Novel Biomarkers ◽

Selection Of

Tumors are the foremost cause of death worldwide. As a result of that, there has been a significant enhancement in the investigation, treatment methods, and good maintenance practices on cancer. However, the sensitivity and specificity of a lot of tumor biomarkers are not adequate. Hence, it is of inordinate significance to ascertain novel biomarkers to forecast the prognosis and therapy targets for tumors. This review characterized LSD1 as a biomarker in different tumors. LSD1 inhibitors in clinical trials were also discussed. The recent pattern advocates that LSD1 is engaged at sauce chromatin zones linking with complexes of multi-protein having an exact DNA-binding transcription factor, establishing LSD1 as a favorable epigenetic target, and also gives a large selection of therapeutic targets to treat different tumors. This review sturdily backing the oncogenic probable of LSD1 in different tumors indicated that LSD1 levels can be used to monitor and identify different tumors and can be a useful biomarker of progression and fair diagnosis in tumor patients. The clinical trials showed that inhibitors of LSD1 have growing evidence of clinical efficacy which is very encouraging and promising. However, for some of the inhibitors such as GSK2879552, though selective, potent, and effective, its disease control was poor as the rate of adverse events (AEs) was high in tumor patients causing clinical trial termination, and continuation could not be supported by the risk-benefit profile. Therefore, we propose that, to attain excellent clinical results of inhibitors of LSD1, much attention is required in designing appropriate dosing regimens, developing in-depth in vitro/in vivo mechanistic works of LSD1 inhibitors, and developing inhibitors of LSD1 that are reversible, safe, potent, and selective which may offer safer profiles.

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