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1.
Biomed Pharmacother ; 148: 112743, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1703121

ABSTRACT

Viral infections are a common cause of morbidity worldwide. The emergence of Coronavirus Disease 2019 (COVID-19) has led to more attention to viral infections and finding novel therapeutics. The CRISPR-Cas9 system has been recently proposed as a potential therapeutic tool for the treatment of viral diseases. Here, we review the research progress in the use of CRISPR-Cas technology for treating viral infections, as well as the strategies for improving the delivery of this gene-editing tool in vivo. Key challenges that hinder the widespread clinical application of CRISPR-Cas9 technology are also discussed, and several possible directions for future research are proposed.


Subject(s)
CRISPR-Cas Systems , Gene Editing/methods , Genetic Therapy/methods , Virus Diseases/therapy , COVID-19/therapy , Genome, Viral , HIV Infections/therapy , Hepatitis B/therapy , Herpesviridae Infections/therapy , Humans , Papillomavirus Infections/therapy , SARS-CoV-2
2.
Biomed Pharmacother ; 146: 112517, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1561313

ABSTRACT

Rapid changes in the viral genome allow viruses to evade threats posed by the host immune response or antiviral drugs, and can lead to viral persistence in the host cells. RNA-dependent RNA polymerase (RdRp) is an essential enzyme in RNA viruses, which is involved in RNA synthesis through the formation of phosphodiester bonds. Therefore, in RNA viral infections such as SARS-CoV-2, RdRp could be a crucial therapeutic target. The present review discusses the promising application of RdRp inhibitors, previously approved or currently being tested in human clinical trials, in the treatment of RNA virus infections. Nucleoside inhibitors (NIs) bind to the active site of RdRp, while nonnucleoside inhibitors (NNIs) bind to allosteric sites. Given the absence of highly effective drugs for the treatment of COVID-19, the discovery of an efficient treatment for this pandemic is an urgent concern for researchers around the world. We review the evidence for molnupiravir (MK-4482, EIDD-2801), an antiviral drug originally designed for Alphavirus infections, as a potential preventive and therapeutic agent for the management of COVID-19. At the beginning of this pandemic, molnupiravir was in preclinical development for seasonal influenza. When COVID-19 spread dramatically, the timeline for development was accelerated to focus on the treatment of this pandemic. Real time consultation with regulators took place to expedite this program. We summarize the therapeutic potential of RdRp inhibitors, and highlight molnupiravir as a new small molecule drug for COVID-19 treatment.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/enzymology , Cytidine/analogs & derivatives , Hydroxylamines/therapeutic use , RNA-Dependent RNA Polymerase/antagonists & inhibitors , Animals , Antiviral Agents/pharmacology , Clinical Trials as Topic/methods , Cytidine/pharmacology , Cytidine/therapeutic use , Humans , Hydroxylamines/pharmacology , RNA-Dependent RNA Polymerase/metabolism
3.
Braz J Infect Dis ; 25(4): 101606, 2021.
Article in English | MEDLINE | ID: covidwho-1442286

ABSTRACT

Since the first described human infection with SARS-CoV-2 in December of 2019 many subunit protein vaccines have been proposed for use in humans. Subunit vaccines use one or more antigens suitable for eliciting a robust immune response. However, the major concern is the efficacy of subunit vaccines and elicited antibodies to neutralize the variants of SARS-CoV-2 like B.1.1.7 (Alpha), B.1.351 (Beta) and P1 (Gamma), B.1.617 (Delta) and C.37 (Lambda). The Spike protein (S) is a potential fragment for use as an antigen in vaccine development. This protein plays a crucial role in the first step of the infection process, as it binds to Angiotensin-Converting Enzyme 2 (ACE2) receptor and enters the host cell after binding. Immunization-induced specific antibodies against the receptor binding domain (RBD) may block and effectively prevent virus invasion. The focus of this review is the impact of spike mutated variants of SARS-CoV2 (Alpha, Beta, Gamma, Delta, and Lambda) on the efficacy of subunit recombinant vaccines. To date, a low or no significant impact on vaccine efficacy against Alpha and Delta variants has been reported. Such an impact on vaccine efficacy for Beta, Delta, Gamma, and Lambda variants may be even greater compared to the Alpha variant. Nonetheless, more comprehensive analyses are needed to assess the real impact on vaccine efficacy brought about by SARS-CoV-2 variants.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Antibodies, Viral , Humans , RNA, Viral , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics , Vaccines, Subunit , Vaccines, Synthetic
4.
Pathol Res Pract ; 221: 153443, 2021 May.
Article in English | MEDLINE | ID: covidwho-1209884

ABSTRACT

Since the outbreak of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the control of virus spread has remained challenging given the pitfalls of the current diagnostic tests. Nevertheless, RNA amplification techniques have been the gold standard among other diagnostic methods for monitoring clinical samples for the presence of the virus. In the current paper, we review the shortcomings and strengths of RT-PCR (real-time polymerase chain reaction) techniques for diagnosis of coronavirus disease (COVID)-19. We address the repercussions of false-negative and false-positive rates encountered in the test, summarize approaches to improve the overall sensitivity of this method. We discuss the barriers to the widespread use of the RT-PCR test, and some technical advances, such as RT-LAMP (reverse-transcriptase-loop mediated isothermal amplification). We also address how other molecular techniques, such as immunodiagnostic tests can be used to avoid incorrect interpretation of RT-PCR tests.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , Real-Time Polymerase Chain Reaction/methods , SARS-CoV-2/isolation & purification , Humans
5.
Int Immunopharmacol ; 97: 107641, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1198829

ABSTRACT

BACKGROUND: When a new pathogen, such as severe acute respiratory syndrome coronavirus 2, appears all novel information can aid in the process of monitoring and in the diagnosis of the coronavirus disease (COVID-19). The aim of the current study is to elucidate the specific miRNA profile which can act as new biomarkers for distinguishing acute COVID-19 disease from the healthy group and those in the post-acute phase of the COVID-19 disease. METHODS: The expression level of selected miRNAs including let-7b-3p, miR-29a-3p, miR-146a-3p and miR-155-5p were evaluated in peripheral blood mononuclear cells (PBMCs) of COVID-19 patients, in both the acute and post-acute COVID-19 phase of the disease and healthy groups, by real-time PCR assays. Specificity and sensitivity of miRNAs was tested by receiver operating characteristic (ROC) analysis in COVID-19 patients. RESULTS: The expression level of all miRNAs in COVID-19 patients was significantly higher than in the healthy group. Therefore, the expression pattern of miR-29a-3p, miR-146a-3p and let-7b-3p in the post-acute COVID-19 phase was significantly different from the acute COVID-19 phase. ROC analyses demonstrated that miR-29a-3p, -155-5p and -146a-3p may serve as the novel biomarker for COVID-19 diagnosis with high specificity and sensitivity. In addition, miR-29a-3p, and -146a-3p can maybe act as novel biomarkers for distinguishing acute from post-acute phase of COVID-19 disease. DISCUSSION: The difference in miRNA expression pattern between COVID-19 patients and those in the healthy group, and between acute COVID-19 with post-acute COVID-19, suggested that cellular miRNAs could be used as promising biomarkers for diagnosis and monitoring of COVID-19.


Subject(s)
COVID-19/blood , COVID-19/diagnosis , Leukocytes, Mononuclear/metabolism , MicroRNAs/biosynthesis , Acute Disease , Adult , Aged , Biomarkers/blood , Female , Gene Expression Profiling , Healthy Volunteers , Humans , Male , Middle Aged , ROC Curve , Real-Time Polymerase Chain Reaction
6.
Int Immunopharmacol ; 97: 107622, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1157433

ABSTRACT

Since September 2020, the world has had more than 28 million cases of coronavirus disease 2019 (COVID-19). Many countries are facing a second wave of the COVID-19 outbreak. A pressing need is evident for the development of a potent vaccine to control the SARS-CoV-2. Institutions and companies in many countries have announced their vaccine research programs and progress against the COVID-19. While most vaccines go through the designation and preparation stages, some of them are under evaluation for efficacy among animal models and clinical trials, and three approved vaccine candidates have been introduced for limited exploitation in Russia and China. An effective vaccine must induce a protective response of both cell-mediated and humoral immunity and should meet the safety and efficacy criteria. Although the emergence of new technologies has accelerated the development of vaccines, there are several challenges on the way, such as limited knowledge about the pathophysiology of the virus, inducing humoral or cellular immunity, immune enhancement with animal coronavirus vaccines, and lack of an appropriate animal model. In this review, we firstly discuss the immune responses against SARS-CoV-2 disease, subsequently, give an overview of several vaccine platforms for SARS-CoV-2 under clinical trials and challenges in vaccine development against this virus.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19 , SARS-CoV-2/immunology , Animals , COVID-19/immunology , COVID-19/prevention & control , COVID-19/therapy , COVID-19 Vaccines/adverse effects , Clinical Trials as Topic , Humans , Immunization, Passive , Reinfection/immunology , SARS-CoV-2/genetics
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