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1.
J Immunol ; 209(2): 280-287, 2022 Jul 15.
Article in English | MEDLINE | ID: covidwho-1964219

ABSTRACT

Hand, foot, and mouth disease (HFMD), which is mainly caused by coxsackievirus A16 (CVA16) or enterovirus A71 (EV-A71), poses a serious threat to children's health. However, the long-term dynamics of the neutralizing Ab (NAb) response and ideal paired-serum sampling time for serological diagnosis of CVA16-infected HFMD patients were unclear. In this study, 336 CVA16 and 253 EV-A71 PCR-positive HFMD inpatients were enrolled and provided 452 and 495 sera, respectively, for NAb detection. Random-intercept modeling with B-spline was conducted to characterize NAb response kinetics. The NAb titer of CVA16 infection patients was estimated to increase from negative (2.1, 95% confidence interval [CI]: 1.4-3.3) on the day of onset to a peak of 304.8 (95% CI: 233.4-398.3) on day 21 and then remained >64 until 26 mo after onset. However, the NAb response level of EV-A71-infected HFMD patients was much higher than that of CVA16-infected HFMD patients throughout. The geometric mean titer was significantly higher in severe EV-A71-infected patients than in mild patients, with a 2.0-fold (95% CI: 1.4-3.2) increase. When a 4-fold rise in titer was used as the criterion for serological diagnosis of CVA16 and EV-A71 infection, acute-phase serum needs to be collected at 0-5 d, and the corresponding convalescent serum should be respectively collected at 17.4 (95% CI: 9.6-27.4) and 24.4 d (95% CI: 15.3-38.3) after onset, respectively. In conclusion, both CVA16 and EV-A71 infection induce a persistent humoral immune response but have different NAb response levels and paired-serum sampling times for serological diagnosis. Clinical severity can affect the anti-EV-A71 NAb response.


Subject(s)
Enterovirus A, Human , Enterovirus Infections , Enterovirus , Hand, Foot and Mouth Disease , Antibodies, Neutralizing , Child , China/epidemiology , Cohort Studies , Hand, Foot and Mouth Disease/diagnosis , Humans , Infant , Longitudinal Studies
2.
ACS omega ; 7(29):25510-25520, 2022.
Article in English | EuropePMC | ID: covidwho-1958148

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) inactivation is an important step toward enhanced biosafety in testing facilities and affords a reduction in the biocontainment level necessary for handling virus-positive biological specimens. Virus inactivation methods commonly employ heat, detergents, or combinations thereof. In this work, we address the dearth of information on the efficacy of SARS-CoV-2 inactivation procedures in plasma and their downstream impact on immunoassays. We evaluated the effects of heat (56 °C for 30 min), detergent (1–5% Triton X-100), and solvent–detergent (SD) combinations [0.3–1% tri-n-butyl phosphate (TNBP) and 1–2% Triton X-100] on 19 immunoassays across different assay formats. Treatments are deemed immunoassay-compatible when the average and range of percentage recovery (treated concentration relative to untreated concentration) lie between 90–110 and 80–120%, respectively. We show that SD treatment (0.3% TNBP/1% Triton-X100) is compatible with more than half of the downstream immunoassays tested and is effective in reducing SARS-CoV-2 infectivity in plasma to below detectable levels in plaque assays. This facile method offers enhanced safety for laboratory workers handling biological specimens in clinical and research settings.

3.
Frontiers in immunology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1919013

ABSTRACT

Striking number of mutations found in the spike protein of recently emerged SARS-CoV-2 Omicron subvariants BA.1, BA.2, BA.3 and BA.4/5 has raised serious concerns regarding the escape from current antibody therapies and vaccine protection. Here, we conducted comprehensive analysis on the extent of two major Omicron lineages BA.1/BA.1.1 and BA.2 to escape neutralization from the therapeutic antibodies approved by the regulatory authorities and convalescent plasma from SARS-CoV-2 patients infected during initial wave of pandemic in early 2020. We showed that Omicron BA.1/BA.1.1 were the most resistant in both magnitude and breadth against antibodies and convalescent plasma, followed by Beta, BA.2, Gamma, Delta and Alpha. While the majority of therapeutic antibodies lost binding and neutralization to Omicron variants, BRII combo (BRII-196 + BRII-198), S309, and AZ combo (COV2-2196 + COV2-2130) maintained neutralization despite of reduction due to either conserved epitope or combinational effect between the two designated antibodies. A single intraperitoneal injection of BRII combo as a prophylactic treatment protected animals from Omicron infection. Treated animals manifested normal body weight, survived infection up to 14 days, undetectable levels of infectious viruses in the lungs, and reduced lung pathology compared to the controls. Analyzing ACE2 from diverse host species showed that Omicron variants acquired ability to use mouse ACE2 for entry. These results demonstrate major antigenic shifts and potentially broadening the host range of two major Omicron lineages BA.1/BA.1.1 and BA.2, posing serious challenges to current antibody therapies and vaccine protection as well as increasing danger of spillover into the wildlife.

4.
Methods Mol Biol ; 2452: 441-464, 2022.
Article in English | MEDLINE | ID: covidwho-1844279

ABSTRACT

The emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents hazards to researchers and other laboratory personnel in research settings where the live virus is stored and handled. The Biosafety Level-3 (BSL-3) Core Facility (CF) at Yong Loo Lin School of Medicine in National University of Singapore (NUS Medicine) has implemented a biorisk management (BRM) system to ensure that biorisk to employees, the public, or the environment are consistently minimized to an acceptable level while working with SARS-CoV-2. This chapter summarizes how a BRM system can be implemented in academic institutions based on international standards in the context of existing local legislations/regulations and institutional policies/guidelines to minimize the risk of laboratory-acquired infections and deliberate misuse of the newly emerged virus, SARS-CoV-2 in BSL-3 laboratories. The BRM programs prioritize performing risk assessments prior to implementation of work processes and reassessing the risk portfolio of the facilities from time to time, determining root causes and prevention of recurrences. Focusing on awareness-raising and educating the laboratory users in biosafety and biosecurity, and identifying opportunities for improvement are the other key factors for a sustainable and successful BRM system in the NUS Medicine BSL-3 CF.


Subject(s)
COVID-19 , SARS-CoV-2 , Containment of Biohazards , Humans , Laboratories , Risk Assessment
5.
Methods Mol Biol ; 2452: 379-391, 2022.
Article in English | MEDLINE | ID: covidwho-1844277

ABSTRACT

Identification of an effective antiviral for the treatment of COVID-19 is considered one of the holy grails in the bid to end the pandemic. However, the novelty of SARS-CoV-2, along with the little knowledge available about its infection characteristics at the beginning of this pandemic, challenges the scientific world on how one may be able to promptly identify promising drug candidates from a myriad of compound libraries. Here, we describe a cytopathic effect (CPE)-based drug screening assay for SARS-CoV-2 which allows for rapid assessment of drug compound libraries through pre- or posttreatment drug screening procedures and evaluation using a light microscope. By comparing the virus-induced CPE of the drug-treated cells against the vehicle and drug controls, potent drug candidates can be quickly identified for further downstream studies.


Subject(s)
COVID-19 , SARS-CoV-2 , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Drug Evaluation, Preclinical , Humans , Pandemics
6.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-332958

ABSTRACT

As SARS-CoV-2 Omicron and other variants of concern continue spreading around the world, development of antibodies and vaccines to confer broad and protective activity is a global priority. Here, we report on the identification of a special group of nanobodies from immunized alpaca with exceptional breadth and potency against diverse sarbecoviruses including SARS-CoV-1, Omicron BA.1, and BA.2. Crystal structure analysis of one representative nanobody, 3-2A2-4, revealed a highly conserved epitope between the cryptic and the outer face of the receptor binding domain (RBD). The epitope is readily accessible regardless of RBD in up or down conformation and distinctive from the receptor ACE2 binding site. Passive delivery of 3-2A2-4 protected K18-hACE2 mice from infection of authentic SARS-CoV-2 Delta and Omicron. This group of nanobodies and the epitope identified should provide invaluable reference for the development of next generation antibody therapies and vaccines against wide varieties of SARS-CoV-2 infection and beyond.

7.
Front Microbiol ; 13: 844447, 2022.
Article in English | MEDLINE | ID: covidwho-1785371

ABSTRACT

The ongoing SARS-CoV-2 pandemic has tested the capabilities of public health and scientific community. Since the dawn of the twenty-first century, viruses have caused several outbreaks, with coronaviruses being responsible for 2: SARS-CoV in 2007 and MERS-CoV in 2013. As the border between wildlife and the urban population continue to shrink, it is highly likely that zoonotic viruses may emerge more frequently. Furthermore, it has been shown repeatedly that these viruses are able to efficiently evade the innate immune system through various strategies. The strong and abundant antiviral innate immunity evasion strategies shown by SARS-CoV-2 has laid out shortcomings in our approach to quickly identify and modulate these mechanisms. It is thus imperative that there be a systematic framework for the study of the immune evasion strategies of these viruses, to guide development of therapeutics and curtail transmission. In this review, we first provide a brief overview of general viral evasion strategies against the innate immune system. Then, we utilize SARS-CoV-2 as a case study to highlight the methods used to identify the mechanisms of innate immune evasion, and pinpoint the shortcomings in the current paradigm with its focus on overexpression and protein-protein interactions. Finally, we provide a recommendation for future work to unravel viral innate immune evasion strategies and suitable methods to aid in the study of virus-host interactions. The insights provided from this review may then be applied to other viruses with outbreak potential to remain ahead in the arms race against viral diseases.

8.
Pharmaceuticals (Basel) ; 15(2)2022 Jan 18.
Article in English | MEDLINE | ID: covidwho-1715602

ABSTRACT

Hand-foot-and-mouth disease (HFMD) caused by human enterovirus A71 (EV-A71) infection has been associated with severe neurological complications. With the lack of an internationally approved antiviral, coupled with a surge in outbreaks globally, EV-A71 has emerged as a neurotropic virus of high clinical importance. Andrographolide has many pharmacological effects including antiviral activity and its derivative, andrographolide sulfonate, has been used in China clinically to treat EV-A71 infections. This study sought to identify novel andrographolide derivatives as EV-A71 inhibitors and elucidate their antiviral mode of action. Using an immunofluorescence-based phenotypic screen, we identified novel EV-A71 inhibitors from a 344-compound library of andrographolide derivatives and validated them with viral plaque assays. Among these hits, ZAF-47, a quinolinoxy-andrographolide, was selected for downstream mechanistic studies. It was found that ZAF-47 acts on EV-A71 post-entry stages and inhibits EV-A71 protein expression. Subsequent luciferase studies confirm that ZAF-47 targets EV-A71 genome RNA replication specifically. Unsuccessful attempts in generating resistant mutants led us to believe a host factor is likely to be involved which coincide with the finding that ZAF-47 exhibits broad-spectrum antiviral activity against other enteroviruses (CV-A16, CV-A6, Echo7, CV-B5, CV-A24 and EV-D68). Furthermore, ZAF-46 and ZAF-47, hits from the screen, were derivatives of the same series containing quinolinoxy and olefin modifications, suggesting that an andrographolide scaffold mounted with these unique moieties could be a potential anti-EV-A71/HFMD strategy.

9.
Clin Infect Dis ; 74(10): 1722-1728, 2022 05 30.
Article in English | MEDLINE | ID: covidwho-1707710

ABSTRACT

BACKGROUND: Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) superspreading events suggest that aerosols play an important role in driving the coronavirus disease 2019 (COVID-19) pandemic. To better understand how airborne SARS-CoV-2 transmission occurs, we sought to determine viral loads within coarse (>5 µm) and fine (≤5 µm) respiratory aerosols produced when breathing, talking, and singing. METHODS: Using a G-II exhaled breath collector, we measured viral RNA in coarse and fine respiratory aerosols emitted by COVID-19 patients during 30 minutes of breathing, 15 minutes of talking, and 15 minutes of singing. RESULTS: Thirteen participants (59%) emitted detectable levels of SARS-CoV-2 RNA in respiratory aerosols, including 3 asymptomatic and 1 presymptomatic patient. Viral loads ranged from 63-5821 N gene copies per expiratory activity per participant, with high person-to-person variation. Patients earlier in illness were more likely to emit detectable RNA. Two participants, sampled on day 3 of illness, accounted for 52% of total viral load. Overall, 94% of SARS-CoV-2 RNA copies were emitted by talking and singing. Interestingly, 7 participants emitted more virus from talking than singing. Overall, fine aerosols constituted 85% of the viral load detected in our study. Virus cultures were negative. CONCLUSIONS: Fine aerosols produced by talking and singing contain more SARS-CoV-2 copies than coarse aerosols and may play a significant role in SARS-CoV-2 transmission. Exposure to fine aerosols, especially indoors, should be mitigated. Isolating viable SARS-CoV-2 from respiratory aerosol samples remains challenging; whether this can be more easily accomplished for emerging SARS-CoV-2 variants is an urgent enquiry necessitating larger-scale studies.


Subject(s)
COVID-19 , Singing , Aerosols , Humans , RNA, Viral/genetics , SARS-CoV-2 , Viral Load
10.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-328866

ABSTRACT

Data on the viral loads in respiratory aerosols from patients infected with Delta and Omicron variants are limited. In this study, we used an exhaled breath bioaerosol collector to collect aerosol samples in coarse (> 5µm) and fine (≤ 5µm) fractions from COVID-19 patients infected with these VOCs while doing various respiratory activities. Samples were tested via SARS-CoV-2 RT-qPCR and virus culture. Nine patients (4 Delta and 5 Omicron) were included. Viral RNA was detectable in seven participants, with greater viral loads in fine aerosols. Notably SARS-CoV-2 RNA was consistently detectable in respiratory samples of all Omicron patients despite them being fully vaccinated and mostly asymptomatic in contrast with Delta patients. Singing and talking without mask generated the greatest viral loads underscoring the transmission potential of SARS-CoV-2 and its variants via respiratory aerosols. The more consistent detection of viral RNA in Omicron-infected patients may account for its greater transmissibility.

11.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-328680

ABSTRACT

Background: On 26 November 2021, the World Health Organization designated the B.1.1.529 lineage of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) as the fifth variant of concern, Omicron. Infections have quickly spread worldwide, but understanding of the viral dynamics and the cytokine and cellular immunological response during infection remain limited. Methods: Detailed patient-level data from 174 age-matched patients with sequence confirmed Omicron or Delta infection admitted to the National Centre for Infectious Diseases, Singapore were analyzed in an observational cohort study. Peripheral blood samples for measurement of SARS-CoV-2 immunological parameters were obtained from a subset. Respiratory samples were collected for viral cultures and correlated to corresponding PCR cycle threshold (Ct) values. Results: Omicron and Delta variant infections in this hospitalized cohort were mild with only 3 (3%) and 14 (16%) developing pneumonia respectively. Omicron infections were more likely to present with sore throat (46.0 vs x23.0%, p=0.005). Neutrophil counts and C-reactive protein (CRP) were significantly lower among the Omicron cohort (Median neutrophil 2.95 [IQR 2.16 – 3.96] vs 4.60 [IQR 3.76 – 6.10] x 10 9 /L , p<0.001;Median CRP 5.7 [IQR 2.0 – 10.0] vs 12.0 [IQR 6.1 – 22.0] mg/L, p<0.001). Trough polymerase chain reaction (PCR) cycle threshold (Ct) values were significantly higher with Omicron infection (17.6 [IQR 16.3 – 19.3] vs 14.9 [IQR 13.9 – 19.0], p=0.001). The pattern and rate of rise in Ct values was similar between Omicron and Delta. At the time of infection, Omicron infected patients had lower levels of pro-inflammatory cytokines Vaccine breakthrough infections with the Omicron variant had a low concentration of proinflammatory cytokines, chemokines, and growth factors at the acute phase of infection, but a more robust IFN-γ response. Less dysregulated immune cell profiles were also observed, including a lower immature neutrophil cell count in Omicron breakthrough cases Conclusions: Omicron infections resulted in mild vaccine breakthrough illness in the majority of patients. Compared with Delta, Omicron infections were more frequently associated with upper respiratory tract infections, had lower viral loads, lower levels of pro-inflammatory cytokines and less dysregulated immune cell profiles.

12.
Viruses ; 14(2)2022 01 24.
Article in English | MEDLINE | ID: covidwho-1648557

ABSTRACT

The constant mutation of SARS-CoV-2 has led to the emergence of new variants, which call for urgent effective therapeutic interventions. The trimeric spike (S) protein of SARS-CoV-2 is highly immunogenic with the receptor-binding domain (RBD) that binds first to the cellular receptor angiotensin-converting enzyme 2 (ACE2) and is therefore the target of many neutralizing antibodies. In this study, we characterized a broadly neutralizing monoclonal antibody (mAb) 9G8, which shows potent neutralization against the authentic SARS-CoV-2 wild-type (WT), Alpha (B.1.1.7), and Delta (1.617.2) viruses. Furthermore, mAb 9G8 also displayed a prominent neutralizing efficacy in the SARS-CoV-2 surrogate virus neutralization test (sVNT) against the Epsilon (B.1.429/7), Kappa (B.1.617.1), Gamma (P.1), Beta (B.1.351), and Delta Plus (1.617.2.1) RBD variants in addition to the variants mentioned above. Based on our in vitro escape mutant studies, we proved that the mutations V483F and Y489H within the RBD were involved in ACE2 binding and caused the neutralizing evasion of the virus from mAb 9G8. The development of such a cross-reactive neutralizing antibody against majority of the SARS-CoV-2 variants provides an important insight into pursuing future therapeutic agents for the prevention and treatment of COVID-19.


Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Serine-Arginine Splicing Factors/immunology , Animals , COVID-19/therapy , COVID-19/virology , Chlorocebus aethiops , Cross Reactions , Epitopes/genetics , Epitopes/immunology , Humans , Mice , Mice, Inbred BALB C , Neutralization Tests , Protein Binding , Serine-Arginine Splicing Factors/genetics , Serine-Arginine Splicing Factors/therapeutic use , Spike Glycoprotein, Coronavirus/immunology , Vero Cells
13.
Front Immunol ; 12: 766821, 2021.
Article in English | MEDLINE | ID: covidwho-1581335

ABSTRACT

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge and spread around the world, antibodies and vaccines to confer broad and potent neutralizing activity are urgently needed. Through the isolation and characterization of monoclonal antibodies (mAbs) from individuals infected with SARS-CoV-2, we identified one antibody, P36-5D2, capable of neutralizing the major SARS-CoV-2 variants of concern. Crystal and electron cryo-microscopy (cryo-EM) structure analyses revealed that P36-5D2 targeted to a conserved epitope on the receptor-binding domain of the spike protein, withstanding the three key mutations-K417N, E484K, and N501Y-found in the variants that are responsible for escape from many potent neutralizing mAbs, including some already approved for emergency use authorization (EUA). A single intraperitoneal (IP) injection of P36-5D2 as a prophylactic treatment completely protected animals from challenge of infectious SARS-CoV-2 Alpha and Beta. Treated animals manifested normal body weight and were devoid of infection-associated death up to 14 days. A substantial decrease of the infectious virus in the lungs and brain, as well as reduced lung pathology, was found in these animals compared to the controls. Thus, P36-5D2 represents a new and desirable human antibody against the current and emerging SARS-CoV-2 variants.


Subject(s)
Antibodies, Monoclonal/pharmacology , Antibodies, Neutralizing/pharmacology , Antibodies, Viral/pharmacology , COVID-19/drug therapy , SARS-CoV-2/drug effects , Animals , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/chemistry , Antibodies, Neutralizing/immunology , Antibodies, Viral/chemistry , Antibodies, Viral/immunology , HEK293 Cells , Humans , Immunization, Passive , Mice
14.
Frontiers in microbiology ; 12, 2021.
Article in English | EuropePMC | ID: covidwho-1562999
15.
Indoor Air ; n/a(n/a), 2021.
Article in English | Wiley | ID: covidwho-1409407

ABSTRACT

Abstract Reliable methods to detect the presence of SARS-CoV-2 at venues where people gather are essential for epidemiological surveillance to guide public policy. Communal screening of air in a highly crowded space has the potential to provide early warning on the presence and potential transmission of SARS-CoV-2 as suggested by studies early in the epidemic. As hospitals and public facilities apply varying degrees of restrictions and regulations, it is important to provide multiple methodological options to enable environmental SARS-CoV-2 surveillance under different conditions. This study assessed the feasibility of using high-flowrate air samplers combined with RNA extraction kit designed for environmental sample to perform airborne SARS-CoV-2 surveillance in hospital setting, tested by RT-qPCR. The success rate of the air samples in detecting SARS-CoV-2 was then compared with surface swab samples collected in the same proximity. Additionally, positive RT-qPCR samples underwent viral culture to assess the viability of the sampled SARS-CoV-2. The study was performed in inpatient ward environments of a quaternary care university teaching hospital in Singapore housing active COVID-19 patients within the period of February to May 2020. Two types of wards were tested, naturally ventilated open-cohort ward and mechanically ventilated isolation ward. Distances between the site of air sampling and the patient cluster in the investigated wards were also recorded. No successful detection of airborne SARS-CoV-2 was recorded when 50 L/min air samplers were used. Upon increasing the sampling flowrate to 150 L/min, our results showed a high success rate in detecting the presence of SARS-CoV-2 from the air samples (72%) compared to the surface swab samples (9.6%). The positive detection rate of the air samples along with the corresponding viral load could be associated with the distance between sampling site and patient. The furthest distance from patient with PCR-positive air samples was 5.5 m. The airborne SARS-CoV-2 detection was comparable between the two types of wards with 60%?87.5% success rate. High prevalence of the virus was found in toilet areas, both on surfaces and in air. Finally, no successful culture attempt was recorded from the environmental air or surface samples.

16.
Front Cell Infect Microbiol ; 11: 700502, 2021.
Article in English | MEDLINE | ID: covidwho-1359165

ABSTRACT

The recent COVID-19 pandemic has highlighted the urgency to develop effective antiviral therapies against the disease. Murine hepatitis virus (MHV) is a coronavirus that infects mice and shares some sequence identity to SARS-CoV-2. Both viruses belong to the Betacoronavirus genus, and MHV thus serves as a useful and safe surrogate model for SARS-CoV-2 infections. Clinical trials have indicated that remdesivir is a potentially promising antiviral drug against COVID-19. Using an in vitro model of MHV infection of RAW264.7 macrophages, the safety and efficacy of monotherapy of remdesivir, chloroquine, ivermectin, and doxycycline were investigated. Of the four drugs tested, remdesivir monotherapy exerted the strongest inhibition of live virus and viral RNA replication of about 2-log10 and 1-log10, respectively (at 6 µM). Ivermectin treatment showed the highest selectivity index. Combination drug therapy was also evaluated using remdesivir (6 µM) together with chloroquine (15 µM), ivermectin (2 µM) or doxycycline (15 µM) - above their IC50 values and at high macrophage cell viability of over 95%. The combination of remdesivir and ivermectin exhibited highly potent synergism by achieving significant reductions of about 7-log10 of live virus and 2.5-log10 of viral RNA in infected macrophages. This combination also resulted in the lowest cytokine levels of IL-6, TNF-α, and leukemia inhibitory factor. The next best synergistic combination was remdesivir with doxycycline, which decreased levels of live virus by ~3-log10 and viral RNA by ~1.5-log10. These results warrant further studies to explore the mechanisms of action of the combination therapy, as well as future in vivo experiments and clinical trials for the treatment of SARS-CoV-2 infection.


Subject(s)
COVID-19 , Coronavirus Infections , Murine hepatitis virus , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Coronavirus Infections/drug therapy , Humans , Ivermectin/pharmacology , Mice , Pandemics , SARS-CoV-2
17.
Pharmacol Ther ; 228: 107930, 2021 12.
Article in English | MEDLINE | ID: covidwho-1281524

ABSTRACT

Traditional drug development and discovery has not kept pace with threats from emerging and re-emerging diseases such as Ebola virus, MERS-CoV and more recently, SARS-CoV-2. Among other reasons, the exorbitant costs, high attrition rate and extensive periods of time from research to market approval are the primary contributing factors to the lag in recent traditional drug developmental activities. Due to these reasons, drug developers are starting to consider drug repurposing (or repositioning) as a viable alternative to the more traditional drug development process. Drug repurposing aims to find alternative uses of an approved or investigational drug outside of its original indication. The key advantages of this approach are that there is less developmental risk, and it is less time-consuming since the safety and pharmacological profile of the repurposed drug is already established. To that end, various approaches to drug repurposing are employed. Computational approaches make use of machine learning and algorithms to model disease and drug interaction, while experimental approaches involve a more traditional wet-lab experiments. This review would discuss in detail various ongoing drug repurposing strategies and approaches to combat the current COVID-19 pandemic, along with the advantages and the potential challenges.


Subject(s)
COVID-19 , Drug Repositioning , Pandemics , COVID-19/drug therapy , COVID-19/epidemiology , Humans
18.
ACS Infect Dis ; 6(7): 1624-1634, 2020 07 10.
Article in English | MEDLINE | ID: covidwho-506087

ABSTRACT

COVID-19 was declared a pandemic by the World Health Organization on March 11, 2020. This novel coronavirus disease, caused by the SARS-CoV-2 virus, has resulted in severe and unprecedented social and economic disruptions globally. Since the discovery of COVID-19 in December 2019, numerous antivirals have been tested for efficacy against SARS-CoV-2 in vitro and also clinically to treat this disease. This review article discusses the main antiviral strategies currently employed and summarizes reported in vitro and in vivo efficacies of key antiviral compounds in use.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus/physiology , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Animals , Antiviral Agents/pharmacology , BCG Vaccine/therapeutic use , Betacoronavirus/chemistry , COVID-19 , Coronavirus Infections/physiopathology , Coronavirus Infections/virology , Drug Repositioning , Host-Pathogen Interactions/drug effects , Host-Pathogen Interactions/immunology , Humans , Immunologic Factors/therapeutic use , Inhibitory Concentration 50 , Measles-Mumps-Rubella Vaccine/therapeutic use , Mice , Pandemics , Pneumonia, Viral/physiopathology , Pneumonia, Viral/virology , SARS-CoV-2 , Treatment Outcome , Virus Replication/drug effects
19.
Chin Herb Med ; 12(3): 207-213, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-459353

ABSTRACT

Members of the China-ASEAN Joint Laboratory for International Cooperation in Traditional Medicine Research used the video conference platform to exchange and discuss the advantages of traditional medicine through the form of score exchange and report, and research and develop the amount and issues of the therapeutic COVID-19 products of concern. This paper mainly reviews the achievements of the implementation of the epidemic prevention and control plan, advances of scientific basic studies on SARS-CoV-2, analysis and screening of potential targets and pathways of antiviral compounds based on network pharmacology and development of antiviral food dual-use products. The authors believe that the declaration of the (10 + 3) special meeting of national leaders on epidemic prevention and control should raise the medical and pharmaceutical issues of common concern. It is the responsibility of our joint laboratory members to accelerate the development of traditional medicine research and industry. Also the authors believe that this exchange will certainly promote the development of the cause of cooperation.

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