J Drug Target. 2021 Dec 2:1-54. doi: 10.1080/1061186X.2021.2013852. Online ahead of print.

ABSTRACT

Covid- 19 is a clinical outcome of viral infection emerged due to strain of beta coronavirus which attacks the type-2 pneumocytes in alveoli via ACE2 receptors. There is no satisfactory drug therapeutic is developed against "SARS-CoV2", highlighting needs of an immediate necessity to give a thorough insight on using chemotherapeutic repurposing plan for the develop COVID-19 infected patients treatment. Drug repurposing is a method of selection of approved therapeutics for new use and is considered to be the most effective drug finding strategy since it includes less time and cost to obtain treatment compared to the no novo drug acquisition process. Several drugs such as hydroxychloroquine, remdesivir, teicoplanin, darunavir, ritonavir, nitoxazide, chloroquine, tocilizumab, and Favipiravir (FPV) showed their activity against "SARS-CoV2" in-vitro and clinical conditions. This review have emphasis on repurposing of drugs, and biologics used in clinical set up for targeting COVID-19 and to evaluate its pharmacokinetics, pharmacodynamics, and safety with their future aspect. The key benefit of drug repurposing is drug is the wealth of information related to its safety, and easy accessibility. Altogether allows for quick access to regulatory approval as well as sophisticated clinical studies.

PMID:34854327 | DOI:10.1080/1061186X.2021.2013852

Brief Bioinform. 2021 Nov 30:bbab467. doi: 10.1093/bib/bbab467. Online ahead of print.

ABSTRACT

MOTIVATION: The development process of a new drug is time-consuming and costly. Thus, identifying new uses for approved drugs, named drug repositioning, is helpful for speeding up the drug development process and reducing development costs. Existing drug-related disease prediction methods mainly focus on single or multiple drug-disease heterogeneous networks. However, heterogeneous networks, and drug subnets and disease subnet contained in heterogeneous networks cover the common topology information between drug and disease nodes, the specific information between drug nodes and the specific information between disease nodes, respectively.

RESULTS: We design a novel model, CTST, to extract and integrate common and specific topologies in multiple heterogeneous networks and subnets. Multiple heterogeneous networks composed of drug and disease nodes are established to integrate multiple kinds of similarities and associations among drug and disease nodes. These heterogeneous networks contain multiple drug subnets and a disease subnet. For multiple heterogeneous networks and subnets, we then define the common and specific representations of drug and disease nodes. The common representations of drug and disease nodes are encoded by a graph convolutional autoencoder with sharing parameters and they integrate the topological relationships of all nodes in heterogeneous networks. The specific representations of nodes are learned by specific graph convolutional autoencoders, respectively, and they fuse the topology and attributes of the nodes in each subnet. We then propose attention mechanisms at common representation level and specific representation level to learn more informative common and specific representations, respectively. Finally, an integration module with representation feature level attention is built to adaptively integrate these two representations for final association prediction. Extensive experimental results confirm the effectiveness of CTST. Comparison with six latest methods and case studies on five drugs further verify CTST has the ability to discover potential candidate diseases.

PMID:34850815 | DOI:10.1093/bib/bbab467

FEBS Open Bio. 2021 Nov 30. doi: 10.1002/2211-5463.13337. Online ahead of print.

ABSTRACT

Cepharanthine is a natural biscoclaurine alkaloid of plant origin and was recently demonstrated to have anti-SARS-CoV-2 activity. In this study, we evaluated whether natural analogues of cepharanthine may act as potential anti-COVID-19 drugs. A total of 24 compounds resembling cepharanthine were extracted from the KNApSAcK database and their binding affinities to target proteins, including the spike protein and main protease of SARS-CoV-2, NPC1 and TPC2 in humans, were predicted via molecular docking simulations. Selected analogues were further evaluated by a cell-based SARS-CoV-2 infection assay. Additionally, the efficacies of cepharanthine and its analogue tetrandrine were assessed. A comparison of the docking conformations of these compounds suggested that the diphenyl ester moiety of the molecules was a putative pharmacophore of the cepharanthine-analogues.

PMID:34850606 | DOI:10.1002/2211-5463.13337

Mol Oncol. 2021 Nov 30. doi: 10.1002/1878-0261.13144. Online ahead of print.

ABSTRACT

Patient-derived organoids are being considered as models that can help guide personalized therapy through in vitro anti-cancer drug response evaluation. However, attempts to quantify in vitro drug responses in organoids and compare them with responses in matched patients remain inadequate. In this study, we investigated whether drug responses of organoids correlate with clinical responses of matched patients and disease progression of patients. Organoids were established from 54 patients with colorectal cancer who (except for one patient) did not receive any form of therapy before, and tumor organoids were assessed through whole-exome sequencing. For comparisons of in vitro drug responses in matched patients, we developed an "organoid score" based on the variable anti-cancer treatment responses observed in organoids. Very interestingly, a higher organoid score was significantly correlated with a lower tumor regression rate after the standard-of-care treatment in matched patients. Additionally, we confirmed that patients with a higher organoid score (≥ 2.5) had poorer progression-free survival compared with those with a lower organoid score (< 2.5). Furthermore, to assess potential drug repurposing using an FDA-approved drug library, ten tumor organoids derived from patients with disease progression were applied to a simulation platform. Taken together, organoids and organoid scores can facilitate the prediction of anti-cancer therapy efficacy, and they can be used as a simulation model to determine the next therapeutic options through drug screening. Organoids will be an attractive platform to enable the implementation of personalized therapy for colorectal cancer patients.

PMID:34850547 | DOI:10.1002/1878-0261.13144

Med Res Rev. 2021 Dec 1. doi: 10.1002/med.21872. Online ahead of print.

ABSTRACT

Auranofin is an oral gold(I) compound, initially developed for the treatment of rheumatoid arthritis. Currently, Auranofin is under investigation for oncological application within a drug repurposing plan due to the relevant antineoplastic activity observed both in vitro and in vivo tumor models. In this review, we analysed studies in which Auranofin was used as a single drug or in combination with other molecules to enhance their anticancer activity or to overcome chemoresistance. The analysis of different targets/pathways affected by this drug in different cancer types has allowed us to highlight several interesting targets and effects of Auranofin besides the already well-known inhibition of thioredoxin reductase. Among these targets, inhibitory-κB kinase, deubiquitinates, protein kinase C iota have been frequently suggested. To rationalize the effects of Auranofin by a system biology-like approach, we exploited transcriptomic data obtained from a wide range of cell models, extrapolating the data deposited in the Connectivity Maps website and we attempted to provide a general conclusion and discussed the major points that need further investigation.

PMID:34850406 | DOI:10.1002/med.21872

Sci Rep. 2021 Nov 30;11(1):23179. doi: 10.1038/s41598-021-02353-5.

ABSTRACT

Since the 2019 novel coronavirus disease (COVID-19) outbreak in 2019 and the pandemic continues for more than one year, a vast amount of drug research has been conducted and few of them got FDA approval. Our objective is to prioritize repurposable drugs using a pipeline that systematically integrates the interaction between COVID-19 and drugs, deep graph neural networks, and in vitro/population-based validations. We first collected all available drugs (n = 3635) related to COVID-19 patient treatment through CTDbase. We built a COVID-19 knowledge graph based on the interactions among virus baits, host genes, pathways, drugs, and phenotypes. A deep graph neural network approach was used to derive the candidate drug's representation based on the biological interactions. We prioritized the candidate drugs using clinical trial history, and then validated them with their genetic profiles, in vitro experimental efficacy, and population-based treatment effect. We highlight the top 22 drugs including Azithromycin, Atorvastatin, Aspirin, Acetaminophen, and Albuterol. We further pinpointed drug combinations that may synergistically target COVID-19. In summary, we demonstrated that the integration of extensive interactions, deep neural networks, and multiple evidence can facilitate the rapid identification of candidate drugs for COVID-19 treatment.

PMID:34848761 | DOI:10.1038/s41598-021-02353-5

Anticancer Res. 2021 Dec;41(12):6061-6065. doi: 10.21873/anticanres.15425.

ABSTRACT

BACKGROUND/AIM: Antimony is a chemical element used in the therapy of parasitic diseases with a promising anticancer potential. The aim of this study was to evaluate in vitro activity of free or liposomal vesicle-packed antimony trioxide (AT or LAT) in the t(15;17)(q22;q21) translocation-positive acute promyelocytic leukemia (APL) cell line NB4.

MATERIALS AND METHODS: Cytotoxicity was analysed with trypan blue exclusion, the MTT assay and neutral red exclusion assay; cell proliferation with PicoGreen®; and reactive oxygen species (ROS) production with DCFDA.

RESULTS: Liposomal particles did not change the pH of the cell culture medium and entered the cells. Both formulations resulted in a time- and concentration-dependent cytotoxicity and production of ROS. LAT showed higher toxicity at lower concentrations compared to AT.

CONCLUSION: LAT may be used to decrease drug dosage and maintain high anti-tumoral effects on APL cells.

PMID:34848460 | DOI:10.21873/anticanres.15425

Anticancer Res. 2021 Dec;41(12):5913-5918. doi: 10.21873/anticanres.15410.

ABSTRACT

The safety windows and toxicity of clinically available known drugs allow drug repurposing to be a popular treatment strategy for several diseases, including cancers. Several common drugs, e.g., metformin, statin, and aspirin are on clinical trials for repurposing in oncology treatment. Most of repurposed drugs, however, cannot be used as single agents and some do not exert any clinically significant effects. The limitations and possible biases from observational studies and preclinical models to repurpose these drugs are debatable. In this article, the limitations and probability of using metformin, one of the most repurposed drugs for cancer treatment and in oncological practice, are discussed.

PMID:34848445 | DOI:10.21873/anticanres.15410

J Med Chem. 2021 Nov 30. doi: 10.1021/acs.jmedchem.1c01333. Online ahead of print.

ABSTRACT

Commonly used non-antibiotic drugs have been associated with changes in gut microbiome composition, paving the way for the possibility of repurposing FDA-approved molecules as next-generation microbiome therapeutics. Herein, we developed and validated an ex vivo high-throughput screening platform─the mini gut model─to underpin human gut microbiome response to molecular modulators. Ten FDA-approved compounds, selected based on maximum structural diversity of molecular fingerprints, were screened against the gut microbiome of five healthy subjects to characterize the ability of human-targeted drugs to modulate the human gut microbiome network. Three compounds, THIP hydrochloride, methenamine, and mesna, have shown promise as novel gut microbiome therapeutics in light of their capability of promoting health-associated features of the gut microbiome. Our findings provide a resource for future research on drug-microbiome interactions and lay the foundation for a new era of more precise gut microbiome modulation through drug repurposing, aimed at targeting specific dysbiotic events.

PMID:34846885 | DOI:10.1021/acs.jmedchem.1c01333

Environ Sci Pollut Res Int. 2021 Nov 30. doi: 10.1007/s11356-021-17824-5. Online ahead of print.

ABSTRACT

Vasoactive intestinal peptide (VIP) is a neuropeptide that is produced by the lymphoid cells and plays a major role in immunological functions for controlling the homeostasis of the immune system. VIP has been identified as a potent anti-inflammatory factor, in boosting both innate and adaptive immunity. Since December 2019, SARS-Cov-2 was found responsible for the disease COVID-19 which has spread worldwide. No specific therapies or 100% effective vaccines are yet available for the treatment of COVID-19. Drug repositioning may offer a strategy and several drugs have been repurposed, including lopinavir/ritonavir, remdesivir, favipiravir, and tocilizumab. This paper describes the main pharmacological properties of synthetic VIP drug (Aviptadil) which is now under clinical trials. A patented formulation of vasoactive intestinal polypeptide (VIP), named RLF-100 (Aviptadil), was developed and finally got approved for human trials by FDA in 2001 and in European medicines agency in 2005. It was awarded Orphan Drug Designation in 2001 by the US FDA for the treatment of acute respiratory distress syndrome and for the treatment of pulmonary arterial hypertension in 2005. Investigational new drug (IND) licenses for human trials of Aviptadil was guaranteed by both the US FDA and EMEA. Preliminary clinical trials seem to support Aviptadil's benefit. However, such drugs like Aviptadil in COVID-19 patients have peculiar safety profiles. Thus, adequate clinical trials are necessary for these compounds.

PMID:34846667 | DOI:10.1007/s11356-021-17824-5

Cancer Med. 2021 Nov 30. doi: 10.1002/cam4.4454. Online ahead of print.

ABSTRACT

BACKGROUND: An open-label single-arm phase 2 study was conducted to evaluate the role of levetiracetam as a sensitizer of concurrent chemoradiotherapy (CCRT) for patients with newly diagnosed glioblastoma. This study aimed to determine the survival benefit of levetiracetam in conjunction with the standard treatment for glioblastoma.

METHODS: Major eligibility requirements included histologically proven glioblastoma in the supratentorial region, patients 18 years or older, and Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Levetiracetam was given at 1,000-2,000 mg daily in two divided doses during CCRT and adjuvant chemotherapy thereafter. The primary and the secondary endpoints were 6-month progression-free survival (6mo-PFS) and 24-month overall survival (24mo-OS), respectively. Outcomes of the study group were compared to those of an external control group.

RESULTS: Between July 2016 and January 2019, 76 patients were enrolled, and 73 patients were included in the final analysis. The primary and secondary outcomes were improved in the study population compared to the external control (6mo-PFS, 84.9% vs. 72.3%, p = 0.038; 24mo-OS, 58.0% vs. 39.9%, p = 0.018), but the differences were less prominent in a propensity score-matched analysis (6mo-PFS, 88.0% vs. 76.9%, p = 0.071; 24mo-OS, 57.1% vs. 38.8%, p = 0.054). In exploratory subgroup analyses, some results suggested that patients with ages under 65 years or unmethylated MGMT promoter might have a greater survival benefit from the use of levetiracetam.

CONCLUSIONS: The use of levetiracetam during CCRT in patients with newly diagnosed glioblastoma may result in improved outcomes, but further investigations are warranted.

PMID:34845868 | DOI:10.1002/cam4.4454

Nat Methods. 2021 Nov 29. doi: 10.1038/s41592-021-01318-w. Online ahead of print.

ABSTRACT

Emergence of new viral agents is driven by evolution of interactions between viral proteins and host targets. For instance, increased infectivity of SARS-CoV-2 compared to SARS-CoV-1 arose in part through rapid evolution along the interface between the spike protein and its human receptor ACE2, leading to increased binding affinity. To facilitate broader exploration of how pathogen-host interactions might impact transmission and virulence in the ongoing COVID-19 pandemic, we performed state-of-the-art interface prediction followed by molecular docking to construct a three-dimensional structural interactome between SARS-CoV-2 and human. We additionally carried out downstream meta-analyses to investigate enrichment of sequence divergence between SARS-CoV-1 and SARS-CoV-2 or human population variants along viral-human protein-interaction interfaces, predict changes in binding affinity by these mutations/variants and further prioritize drug repurposing candidates predicted to competitively bind human targets. We believe this resource ( http://3D-SARS2.yulab.org ) will aid in development and testing of informed hypotheses for SARS-CoV-2 etiology and treatments.

PMID:34845387 | DOI:10.1038/s41592-021-01318-w

J Biomol Struct Dyn. 2021 Nov 30:1-10. doi: 10.1080/07391102.2021.2009033. Online ahead of print.

ABSTRACT

COVID-19 is caused by SARS-CoV-2 and responsible for the ongoing global pandemic in the world. After more than a year, we are still in lurch to combat and control the situation. Therefore, new therapeutic options to control the ongoing COVID-19 are urgently in need. In our study, we found that nonstructural protein 4 (Nsp4) of SARS-CoV-2 could be a potential target for drug repurposing. Due to availability of only the crystal structure of C-terminal domain of Nsp4 (Ct-Nsp4) and its crucial participation in viral RNA synthesis, we have chosen Ct-Nsp4 as a target for screening the 1600 FDA-approved drugs using molecular docking. Top 102 drugs were found to have the binding energy equal or less than -7.0 kcal/mol. Eribulin and Suvorexant were identified as the two most promising drug molecules based on the docking score. The dynamics of Ct-Nsp4-drug binding was monitored using 100 ns molecular dynamics simulations. From binding free energy calculation over the simulation, both the drugs were found to have considerable binding energy. The present study has identified Eribulin and Suvorexant as promising drug candidates. This finding will be helpful to accelerate the drug discovery process against COVID-19 disease.Communicated by Ramaswamy H. Sarma.

PMID:34844509 | DOI:10.1080/07391102.2021.2009033

Antiviral Res. 2021 Nov 24;197:105212. doi: 10.1016/j.antiviral.2021.105212. Online ahead of print.

ABSTRACT

Drug repositioning has been used extensively since the beginning of the COVID-19 pandemic in an attempt to identify antiviral molecules for use in human therapeutics. Hydroxychloroquine and azithromycin have shown inhibitory activity against SARS-CoV-2 replication in different cell lines. Based on such in vitro data and despite the weakness of preclinical assessment, many clinical trials were set up using these molecules. In the present study, we show that hydroxychloroquine and azithromycin alone or combined does not block SARS-CoV-2 replication in human bronchial airway epithelia. When tested in a Syrian hamster model, hydroxychloroquine and azithromycin administrated alone or combined displayed no significant effect on viral replication, clinical course of the disease and lung impairments, even at high doses. Hydroxychloroquine quantification in lung tissues confirmed strong exposure to the drug, above in vitro inhibitory concentrations. Overall, this study does not support the use of hydroxychloroquine and azithromycin as antiviral drugs for the treatment of SARS-CoV-2 infections.

PMID:34838583 | DOI:10.1016/j.antiviral.2021.105212

J Pharm Biomed Anal. 2021 Nov 23:114469. doi: 10.1016/j.jpba.2021.114469. Online ahead of print.

ABSTRACT

Neglected tropical diseases (NTDs) such as visceral leishmaniasis (VL) present a limited and toxic therapeutic arsenal, and drug repositioning represents a safe and cost-effective approach. In this work, we investigated the antileishmanial potential and the mechanism of lethal action of the antidepressant escitalopram. The efficacy of escitalopram was determined ex-vivo using the intracellular Leishmania (L.) infantum amastigote model and the mammalian cytotoxicity was determined by the colorimetric MTT assay. The cellular and molecular alterations induced by the drug were investigated using spectrofluorimetry, a luminescence assay and flow cytometry. Our data revealed that escitalopram was active and selective against L. infantum parasites, with an IC50 value of 25 µM and a 50% cytotoxic concentration (CC50) of 184 µM. By using the fluorescent probes SYTOX® Green and DiSBAC2(3), the drug showed no alterations in the plasma membrane permeability nor in the electric potential of the membrane (∆ψp); however, after a short-time incubation, the drug caused a dose-dependent up-regulation of the calcium levels, leading to the depolarization of the mitochondrial membrane potential (∆ψm) and a reduction of the ATP levels. No up-regulation of reactive oxygen (ROS) was observed. In the cell cycle analysis, escitalopram induced a dose-dependent increase of the parasites at the sub G0/G1 stage, representing fragmented DNA. Escitalopram presented a selective antileishmanial activity, with disruption of single mitochondrion and interference in the cell cycle. Approved drugs such as escitalopram may represent a promising approach for NTDs and can be considered in future animal efficacy studies.

PMID:34838348 | DOI:10.1016/j.jpba.2021.114469

Neuromolecular Med. 2021 Nov 27. doi: 10.1007/s12017-021-08697-5. Online ahead of print.

ABSTRACT

Neuroprotective, antineuroinflammatory, and proneurogenic effects of glucosamine, a naturally occurring amino sugar, have been reported in various animal models of brain injury including cerebral ischemia and hypoxic brain damage. Given that clinical translation of therapeutic candidates identified in animal models of ischemic stroke has remained unsatisfactory in general, possibly due to inadequacy of existing models, we sought to study the effects of glucosamine in a recently developed, clinical condition mimicking mouse model of internal cerebral artery occlusion. In this model of mild to moderate striatal damage, glucosamine ameliorated behavioral dysfunction, rescued ischemia-induced striatal damage, and suppressed ischemia-induced upregulation of proinflammatory genes in striatal tissue. Further, in ex vivo neurosphere assay involving neural stem cells/neural progenitor cells from subventricular zone, glucosamine increased the number of large neurospheres, along with enhancing mRNA levels of the proliferation markers Nestin, NeuroD1, and Sox2. Lastly, coronal brain sections containing the striatal region with subventricular zone showed increased number of BrdU positive cells and DCX positive cells, a marker for newly differentiating and immature neurons, in glucosamine-treated ischemic mice. Cumulatively, the results confirming neuroprotective, antineuroinflammatory, and proneurogenic effects of glucosamine enhance drug repurposing potential of glucosamine in cerebral ischemia.

PMID:34837638 | DOI:10.1007/s12017-021-08697-5

Intern Med J. 2021 Nov 27. doi: 10.1111/imj.15635. Online ahead of print.

ABSTRACT

BACKGROUND: In 2018, an innovative, State government funded cannabis medicines drug information service was established for health professionals in New South Wales (NSW). The NSW Cannabis Medicines Advisory Service (CMAS) provides expert clinical guidance and support to medical practitioners considering prescribing a cannabis medicine to their patient(s).

AIMS: This research examines quality assurance and patient outcomes related to enquirers' experience with NSW CMAS.

METHODS: Data collection involved an online, anonymous survey with two components. Following a health professional enquiry, quality assurance data was collected about the enquirers' experience with NSW CMAS. The second survey focused on patient outcomes and provides real-world observational data about cannabis medicines safety and effectiveness across a wide range of indications.

RESULTS: Data collection occurred between January 2020 and June 2021. Preliminary analyses were based on 68 quality assurance and 50 patient outcomes survey responses. General practitioners represented the highest proportion of survey responses (n = 33, 49%). The most common enquiry involved 'patient-specific advice' (n = 50, 74%). Patient-specific information provided by the service was mainly used for prescribing decision support (n = 45, 90%).

CONCLUSIONS: Preliminary findings highlight the impact of an innovative cannabis medicines drug information service in supporting health professional clinical practice in an area of rapid knowledge translation. Quality assurance data indicates that the service is perceived well by the majority of enquirers. Patient outcomes data across a wide range of indications suggest some effectiveness and a reasonable safety profile for prescribed cannabis medicines for most patients. This article is protected by copyright. All rights reserved.

PMID:34837455 | DOI:10.1111/imj.15635

Lab Invest. 2021 Nov 26. doi: 10.1038/s41374-021-00704-4. Online ahead of print.

ABSTRACT

Mesenchymal chondrosarcoma (MCS) is a high-grade malignancy that represents 2-9% of chondrosarcomas and mostly affects children and young adults. HEY1-NCoA2 gene fusion is considered to be a driver of tumorigenesis and it has been identified in 80% of MCS tumors. The shortage of MCS samples and biological models creates a challenge for the development of effective therapeutic strategies to improve the low survival rate of MCS patients. Previous molecular studies using immunohistochemical staining of patient samples suggest that activation of PDGFR signaling could be involved in MCS tumorigenesis. This work presents the development of two independent in vitro and in vivo models of HEY1-NCoA2-driven MCS and their application in a drug repurposing strategy. The in vitro model was characterized by RNA sequencing at the single-cell level and successfully recapitulated relevant MCS features. Imatinib, as well as specific inhibitors of ABL and PDGFR, demonstrated a highly selective cytotoxic effect targeting the HEY1-NCoA2 fusion-driven cellular model. In addition, patient-derived xenograft (PDX) models of MCS harboring the HEY1-NCoA2 fusion were developed from a primary tumor and its distant metastasis. In concordance with in vitro observations, imatinib was able to significantly reduce tumor growth in MCS-PDX models. The conclusions of this study serve as preclinical results to revisit the clinical efficacy of imatinib in the treatment of HEY1-NCoA2-driven MCS.

PMID:34837064 | DOI:10.1038/s41374-021-00704-4

Nutrients. 2021 Oct 26;13(11):3801. doi: 10.3390/nu13113801.

ABSTRACT

Pancreatic cancer, the seventh most lethal cancer around the world, is considered complicated cancer due to poor prognosis and difficulty in treatment. Despite all the conventional treatments, including surgical therapy and chemotherapy, the mortality rate is still high. Therefore, the possibility of using natural products for pancreatic cancer is increasing. In this study, 68 natural products that have anti-pancreatic cancer effects reported within five years were reviewed. The mechanisms of anti-cancer effects were divided into four types: apoptosis, anti-metastasis, anti-angiogenesis, and anti-resistance. Most of the studies were conducted for natural products that induce apoptosis in pancreatic cancer. Among them, plant extracts such as Eucalyptus microcorys account for the major portion. Some natural products, including Moringa, Coix seed, etc., showed multi-functional properties. Natural products could be beneficial candidates for treating pancreatic cancer.

PMID:34836055 | DOI:10.3390/nu13113801

Vaccines (Basel). 2021 Nov 12;9(11):1317. doi: 10.3390/vaccines9111317.

ABSTRACT

Respiratory viruses represent a major public health concern, as they are highly mutated, resulting in new strains emerging with high pathogenicity. Currently, the world is suffering from the newly evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus is the cause of coronavirus disease 2019 (COVID-19), a mild-to-severe respiratory tract infection with frequent ability to give rise to fatal pneumonia in humans. The overwhelming outbreak of SARS-CoV-2 continues to unfold all over the world, urging scientists to put an end to this global pandemic through biological and pharmaceutical interventions. Currently, there is no specific treatment option that is capable of COVID-19 pandemic eradication, so several repurposed drugs and newly conditionally approved vaccines are in use and heavily applied to control the COVID-19 pandemic. The emergence of new variants of the virus that partially or totally escape from the immune response elicited by the approved vaccines requires continuous monitoring of the emerging variants to update the content of the developed vaccines or modify them totally to match the new variants. Herein, we discuss the potential therapeutic and prophylactic interventions including repurposed drugs and the newly developed/approved vaccines, highlighting the impact of virus evolution on the immune evasion of the virus from currently licensed vaccines for COVID-19.

PMID:34835248 | DOI:10.3390/vaccines9111317