- Next generation infection prevention clothing: Non-woven Fabrics Coated with Cranberry Extracts Capable of Inactivating Enveloped Viruses such as SARS-CoV-2 and Multidrug-resistant Bacteria -
The Coronavirus Disease (COVID-19) pandemic is demanding rapid action of the authorities and scientific community in order to find new antimicrobial solutions that could inactivate the pathogen SARS-CoV-2 that causes this disease. Gram-positive bacteria contribute to severe pneumonia associated with COVID-19, and their resistance to antibiotics is increasing at an alarming rate. In this regard, non-woven fabrics are currently used for the fabrication of infection prevention clothing such as face masks, caps, scrubs, shirts, trousers, disposable gowns, overalls, hoods, aprons and shoe covers as protective tools against viral and bacterial infections. However, these non-woven fabrics are made of materials that do not possess antimicrobial activity. Thus, we have developed here non-woven fabrics with antimicrobial coatings of cranberry extracts capable of inactivating enveloped viruses such as SARS-CoV-2 and the phage phi 6, and two multidrug-resistant bacteria: the methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. The non- toxicity of these advanced technology was ensured using a Caenorhabditis elegans in vivo model. These results open up a new prevention path using natural and biodegradable compounds for the fabrication of infection prevention clothing in the current COVID-19 and future pandemics.
- **Molecular basis of a dominant SARS-CoV-2 Spike-derived epitope presented by HLA-A*02:01 recognised by a public TCR** -
The data currently available on how the immune system recognizes the SARS-CoV-2 virus is growing rapidly. While there are structures of some SARS-CoV-2 proteins in complex with antibodies, which helps us understand how the immune system is able to recognise this new virus, we are lacking data on how T cells are able to recognize this virus. T cells, especially the cytotoxic CD8+ T cells, are critical for viral recognition and clearance. Here we report the X-ray crystallography structure of a T cell receptor, shared among unrelated individuals (public TCR) in complex with a dominant spike-derived CD8+ T cell epitope (YLQ peptide). We show that YLQ activates a polyfunctional CD8+ T cell response in COVID-19 recovered patients. We detail the molecular basis for the shared TCR gene usage observed in HLA-A*02:01+ individuals, providing an understanding of TCR recognition towards a SARS-CoV-2 epitope. Interestingly, the YLQ peptide conformation did not change upon TCR binding, facilitating the high-affinity interaction observed.
- A time irreversible model of nucleotide substitution for the coronavirus evolution -
SARS-CoV-2 is the cause of the worldwide epidemic of severe acute respiratory syndrome. Evolutionary studies of the virus genome will provide a predictor of the fate of COVID-19 in the near future. Recent studies of the virus genomes have shown that C to U substitutions are overrepresented in the genome sequences of SARS-CoV-2. Traditional time- reversible substitution models cannot be applied to the evolution of SARS-CoV-2 sequences. Therefore, in this study, I propose a new time-irreversible model and a new method for estimating the nucleotide substitution rate of SARS-CoV-2. Computer simulations showed that that the new method gives good estimates. I applied the new method to estimate nucleotide substitution rates of SARS-CoV-2 sequences. The result suggests that the rate of C to U substitution of SARS- Cov-2 is ten times higher than other types of substitutions.
- Mutations in SARS-CoV-2 Variants Modulate the Microscopic Dynamics of Neutralizing Antibodies -
Monoclonal antibodies have emerged as viable treatment for the COVID-19 disease caused by the SARS-CoV-2 virus. But the new viral variants can reduce the efficacy of the currently available antibodies, as well as diminish the vaccine induced immunity. Here, we demonstrate how the microscopic dynamics of the SARS-CoV-2 neutralizing monoclonal antibodies, can be modulated by the mutations present in the spike proteins of the variants currently circulating in the world population. We show that the dynamical perturbation in the antibody structure can be diverse, depending both on the nature of the antibody and on the location of the mutation. The correlated motion between the antibody and the receptor binding domain (RBD) can also be changed, altering the binding affinity. By constructing a protein graph connectivity network, we could delineate the mutant induced modifications in the allosteric information flow pathway through the antibody, and observed the presence of both localized and long distance effects. We identified a loop consisting of residues 470-490 in the RBD which works like an anchor preventing the detachment of the antibodies, and individual mutations in that region can significantly affect the antibody binding propensity. Our study provides fundamental and atomistically detailed insight on how virus neutralization by monoclonal antibody can be impacted by the mutations in the epitope, and can potentially facilitate the rational design of monoclonal antibodies, effective against the new variants of the novel coronavirus.
- Cutting epitopes to survive: the case of lambda variant -
This manuscript concisely reports an in-silico study on the potential impact of the Spike protein mutations on immuno-escape ability of SARS-CoV-2 lambda variant. Biophysical and bioinformatics data suggest that a combination of shortening immunogenic epitope loops and generation of potential N-glycosylation sites may be a viable adaptation strategy potentially allowing this emerging viral variant escaping host immunity.
- SMOG 2 and OpenSMOG: Extending the limits of structure-based models -
Applying simulations with structure-based (Go-like) models has proven to be an effective strategy for investigating the factors that control biomolecular dynamics. The common element of these models is that some (or all) of the intra/inter-molecular interactions are explicitly defined to stabilize an experimentally-determined structure. To facilitate the development and application of this broad class of models, we previously released the SMOG 2 software package. This suite allows one to easily customize and distribute structure-based (i.e. SMOG) models for any type of polymer-ligand system. Since its original release, user feedback has driven the implementation of numerous enhancements. Here, we describe recent extensions to the software and demonstrate the capabilities of the most recent version, SMOG v2.4. Changes include new tools that aid user-defined customization of force fields, as well as an interface with the OpenMM simulation libraries (OpenSMOG v1.0). To illustrate the utility of these advances, we present several applications of SMOG2 and OpenSMOG, which include systems with millions of atoms, long polymers and explicit ions. We also highlight how one can incorporate non-structure-based (e.g. AMBER-based) energetics to define a hybrid class of models. The representative applications include large-scale rearrangements of the SARS-CoV-2 Spike protein, the HIV-1 capsid in the presence of explicit ions, and crystallographic lattices of ribosomes and proteins. In summary, SMOG 2 and OpenSMOG provide robust support for researchers who seek to apply structure-based models to large and/or intricate biomolecular systems.
- ImputeCoVNet: 2D ResNet Autoencoder for Imputation of SARS-CoV-2 Sequences -
We describe a new deep learning approach for the imputation of SARS-CoV-2 variants. Our model, ImputeCoVNet, consists of a 2D ResNet Autoencoder that aims at imputing missing genetic variants in SARS-CoV-2 sequences in an efficient manner. We show that ImputeCoVNet leads to accurate results at minor allele frequencies as low as 0.0001. When compared with an approach based on Hamming distance, ImputeCoVNet achieved comparable results with significantly less computation time. We also present the provision of geographical metadata (e.g., exposed country) to decoder increases the imputation accuracy. Additionally, by visualizing the embedding results of SARS-CoV-2 variants, we show that the trained encoder of ImputeCoVNet, or the embedded results from it, recapitulates viral clade’s information, which means it could be used for predictive tasks using virus sequence analysis.
- Antiviral face mask functionalized with solidified hand soap: low-cost infection prevention clothing against enveloped viruses such as SARS-CoV-2 -
Infection prevention clothing is becoming an essential protective tool in the current pandemic, especially because now we know that SARS-CoV-2 can easily infect humans in poorly ventilated indoor spaces. However, commercial infection prevention clothing is made of fabrics that are not capable of inactivating the virus. Therefore, viral infections of symptomatic and asymptomatic individuals wearing protective clothing such as masks can occur through aerosol transmission or by contact with the contaminated surfaces of the masks, which are suspected as an increasing source of highly infectious biological waste. Herein, we report an easy fabrication method of a novel antiviral non-woven fabric containing polymer filaments that were coated with solidified hand soap. This extra protective fabric is capable of inactivating enveloped viruses such as SARS-CoV-2 and phi 6 in one minute of contact. In this study, this antiviral fabric was used to fabricate an antiviral face mask and did not show any cytotoxic effect in human keratinocyte HaCaT cells. Furthermore, this antiviral non-woven fabric could be used for the fabrication of other infection prevention clothing such as caps, scrubs, shirts, trousers, disposable gowns, overalls, hoods, aprons, and shoe covers. Therefore, this low-cost technology could provide a wide range of infection protective tools to combat COVID-19 and future pandemics in developed and underdeveloped countries.
- Peptide Scanning of SARS-CoV and SARS-CoV-2 Spike Protein Subunit 1 Reveals Potential Additional Receptor Binding Sites -
The binding of SARS-CoV and SARS-CoV-2 to the ACE2 receptor on human cells is mediated by the spike protein subunit 1 (S1) on the virus surfaces, while the receptor binding domains (RBDs) of S1 are the major determinants for the interaction with ACE2 and dominant targets of neutralizing antibodies. However, at the virus-host interface, additional biomolecular interactions, although being relatively weak in affinity and low in specificity, could also contribute to viral attachment and play important roles in gain- or loss-of-function mutations. In this work, we performed a peptide scanning of the S1 domains of SARS-CoV and SARS-CoV-2 by synthesizing 972 16-mer native and mutated peptide fragments using a high throughput in situ array synthesis technology. By probing the array using fluorescently labelled ACE2, a number of previously unknown potential receptor binding sites of S1 have been revealed. 20 peptides were synthesized using solid phase peptide synthesis, in order to validate and quantify their binding to ACE2. Four ACE2-binding peptides were selected, to investigate whether they can be assembled through a biotinylated peptide/neutravidin system to achieve high affinity to ACE2. A number of constructs exhibited high affinity to ACE2 with Kd values of pM to low nM.
- Age-related susceptibility of ferrets to SARS-CoV-2 infection -
Susceptibility to SARS-CoV-2 and the outcome of COVID-19 have been linked to underlying health conditions and the age of affected individuals. Here we assessed the effect of age on SARS-CoV-2 infection using a ferret model. For this, young (6-month-old) and aged (18-to-39-month-old) ferrets were inoculated intranasally with various doses of SARS-CoV-2. By using infectious virus shedding in respiratory secretions and seroconversion, we estimated that the infectious dose of SARS-CoV-2 in aged animals is ~32 plaque forming units (PFU) per animal while in young animals it was estimated to be ~100 PFU. We showed that viral replication in the upper respiratory tract and shedding in respiratory secretions is enhanced in aged ferrets when compared to young animals. Similar to observations in humans, this was associated with higher expressions levels of two key viral entry factors - ACE2 and TMPRSS2 - in the upper respiratory tract of aged ferrets.
- A screening pipeline identifies a broad-spectrum inhibitor of bacterial AB toxins with cross protection against influenza A virus H1N1 and SARS-CoV-2 -
A challenge for the development of host-targeted anti-infectives against a large spectrum of AB-like toxin- producing bacteria encompasses the identification of chemical compounds corrupting toxin transport through both endolysosomal and retrograde pathways. Here, we performed a high-throughput screening of small chemical compounds blocking active Rac1 proteasomal degradation triggered by the Cytotoxic Necrotizing Factor-1 (CNF1) toxin, followed by orthogonal screens against two AB toxins hijacking defined endolysosomal (Diphtheria toxin) or retrograde (Shiga-like toxin 1) pathways to intoxicate cells. This led to the identification of the molecule N-(3,3-diphenylpropyl)-1-propyl-4-piperidinamine, referred to as C910. This compound induces the swelling of EEA1-positive early endosomes, in absence of PIKfyve kinase inhibition, and disturbs the trafficking of CNF1 and the B-subunit of Shiga toxin along the endolysosomal or retrograde pathways, respectively. Together, we show that C910 protects cells against 8 bacterial AB toxins including large clostridial glucosylating toxins from Clostridium difficile. Of interest, C910 also reduced viral infection in vitro including influenza A virus subtype H1N1 and SARS- CoV-2. Moreover, parenteral administration of C910 to the mice resulted in its accumulation in lung tissues and reduced lethal influenza infection.
- Infection and transmission of SARS-CoV-2 and its alpha variant in pregnant white-tailed deer -
SARS-CoV-2, a novel Betacoronavirus, was first reported circulating in human populations in December 2019 and has since become a global pandemic. Recent history involving SARS-like coronavirus outbreaks (SARS-CoV and MERS-CoV) have demonstrated the significant role of intermediate and reservoir hosts in viral maintenance and transmission cycles. Evidence of SARS-CoV-2 natural infection and experimental infections of a wide variety of animal species has been demonstrated, and in silico and in vitro studies have indicated that deer are susceptible to SARS-CoV-2 infection. White-tailed deer (Odocoileus virginianus) are amongst the most abundant, densely populated, and geographically widespread wild ruminant species in the United States. Human interaction with white-tailed deer has resulted in the occurrence of disease in human populations in the past. Recently, white-tailed deer fawns were shown to be susceptible to SARS-CoV-2. In the present study, we investigated the susceptibility and transmission of SARS-CoV-2 in adult white- tailed deer. In addition, we examined the competition of two SARS-CoV-2 isolates, representatives of the ancestral lineage A (SARS-CoV-2/human/USA/WA1/2020) and the alpha variant of concern (VOC) B.1.1.7 (SARS- CoV-2/human/USA/CA_CDC_5574/2020), through co-infection of white-tailed deer. Next-generation sequencing was used to determine the presence and transmission of each strain in the co-infected and contact sentinel animals. Our results demonstrate that adult white-tailed deer are highly susceptible to SARS-CoV-2 infection and can transmit the virus through direct contact as well as vertically from doe to fetus. Additionally, we determined that the alpha VOC B.1.1.7 isolate of SARS-CoV-2 outcompetes the ancestral lineage A isolate in white-tailed deer, as demonstrated by the genome of the virus shed from nasal and oral cavities from principal infected and contact animals, and from virus present in tissues of principal infected deer, fetuses and contact animals.
- Comparison of Wild Type DNA Sequence of Spike Protein from SARS-CoV-2 with Optimized Sequence on The Induction of Protective Responses Against SARS-Cov-2 Challenge in Mouse Model -
COVID-19 caused by SARS-CoV-2 has been spreading worldwide. To date, several vaccine candidates moved into EUA or CA applications. Although DNA vaccine is on phase III clinical trial, it is a promised technology platform with many advantages. Here, we showed that the pGX9501 DNA vaccine encoded the spike full-length protein-induced strong humoral and cellular immune responses in mice with higher neutralizing antibodies, blocking the hACE2-RBD binding against live virus infection in vitro. Importantly, higher levels of IFN-{gamma} expression in CD8+ and CD4+ T cell and specific cytotoxic lymphocyte (CTL) killings effect were also observed in the pGX9501-immunized group. It provided subsequent protection against virus challenges in the hACE2 transgenic mouse model. Overall, pGX9501 was a promising DNA vaccine candidate against COVID-19, inducing strong humoral immunity and cellular immunity that contributed to the vaccine’s protective effects.
- Optimization of Non-Coding Regions Improves Protective Efficacy of an mRNA SARS-CoV-2 Vaccine in Nonhuman Primates -
The CVnCoV (CureVac) mRNA vaccine for SARS-CoV-2 has recently been evaluated in a phase 2b/3 efficacy trial in humans. CV2CoV is a second-generation mRNA vaccine with optimized non-coding regions and enhanced antigen expression. Here we report a head-to-head study of the immunogenicity and protective efficacy of CVnCoV and CV2CoV in nonhuman primates. We immunized 18 cynomolgus macaques with two doses of 12 ug of lipid nanoparticle formulated CVnCoV, CV2CoV, or sham (N=6/group). CV2CoV induced substantially higher binding and neutralizing antibodies, memory B cell responses, and T cell responses as compared with CVnCoV. CV2CoV also induced more potent neutralizing antibody responses against SARS-CoV-2 variants, including B.1.351 (beta), B.1.617.2 (delta), and C.37 (lambda). While CVnCoV provided partial protection against SARS-CoV-2 challenge, CV2CoV afforded robust protection with markedly lower viral loads in the upper and lower respiratory tract. Antibody responses correlated with protective efficacy. These data demonstrate that optimization of non-coding regions can greatly improve the immunogenicity and protective efficacy of an mRNA SARS- CoV-2 vaccine in nonhuman primates.
- Surfacing norms to increase vaccine acceptance -
Despite the availability of multiple safe vaccines, vaccine hesitancy may present a challenge to successful control of the COVID-19 pandemic. As with many human behaviors, people’s vaccine acceptance may be affected by their beliefs about whether others will accept a vaccine (i.e., descriptive norms). However, information about these descriptive norms may have different effects depending on people’s baseline beliefs and the relative importance of conformity, social learning, and free-riding. Here, using a large, pre-registered, randomized experiment (N=437,236) embedded in an international survey, we show that accurate information about descriptive norms can substantially increase intentions to accept a vaccine for COVID-19. These positive effects (e.g., reducing by 5.3% the fraction of people who are “unsure” or more negative about accepting a vaccine) are largely consistent across the 23 included countries, but are concentrated among people who were otherwise uncertain about accepting a vaccine. Providing this normative information in vaccine communications partially corrects individuals’ apparent underestimation of how many other people will accept a vaccine. These results suggest that public health communications should present information about the widespread and growing intentions to accept COVID-19 vaccines.
Pulmonary Rehabilitation Post-COVID-19 - Condition: COVID-19
Intervention: Other: Exercise program (virtual/remote)
Sponsors: University of Manitoba; Health Sciences Centre Foundation, Manitoba; Health Sciences Centre, Winnipeg, Manitoba
Not yet recruiting
To Evaluate Efficacy & Safety of Proxalutamide in Hospitalized Covid-19 Subjects - Condition: Covid19
Interventions: Drug: GT0918; Drug: Standard of care; Drug: Matching placebo
Sponsors: Suzhou Kintor Pharmaceutical Inc,; IQVIA Biotech
Not yet recruiting
Study of Allogeneic Adipose-Derived Mesenchymal Stem Cells to Treat Post COVID-19 “Long Haul” Pulmonary Compromise - Condition: Covid19
Interventions: Biological: COVI-MSC; Biological: Placebo
Sponsor: Sorrento Therapeutics, Inc.
Not yet recruiting
Mix and Match Heterologous Prime-Boost Study Using Approved COVID-19 Vaccines in Mozambique - Condition: Covid19
Interventions: Biological: BBIBP-CorV - Inactivated SARS-CoV-2 vaccine (Vero cell); Biological: AZD1222 (replication-deficient Ad type 5 vector expressing full-length spike protein)
Sponsors: International Vaccine Institute; The Coalition for Epidemic Preparedness Innovations (CEPI); Instituto Nacional de Saúde (INS), Mozambique; University of Antananarivo; International Centre for Diarrhoeal Disease Research, Bangladesh; Harvard University; Heidelberg University
Not yet recruiting
Targeting de Novo Pyrimidine Biosynthesis by Leflunomide for the Treatment of COVID-19 Virus Disease - Condition: COVID-19
Intervention: Drug: leflunomide
Sponsor:
Ashford and St. Peter’s Hospitals NHS Trust
Active, not recruiting
Double Blind Randomized Clinical Trial of Use of Colchicine Added to Standard Treatment in Hospitalized With Covid-19 - Condition: COVID-19 Infection
Intervention: Drug: Colchcine
Sponsor:
Asociacion Instituto Biodonostia
Active, not recruiting
ACTIV-5 / Big Effect Trial (BET-C) for the Treatment of COVID-19 - Condition: COVID-19
Interventions: Drug: Danicopan; Other: Placebo; Drug: Remdesivir
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Recruiting
COVID-19 Methylene Blue Antiviral Treatment - Condition: Covid19
Interventions: Drug: Methylene Blue; Drug: Saline nasal spray
Sponsors: Irkutsk Scientific Center of the Siberian Branch of the Russian Academy of Sciences; Irkutsk State Medical University
Recruiting
Project FLUx COntact-CoVID-19 Faculty of Medicine Paris-Saclay - Condition: Covid19
Interventions: Other: Antigenic tests (on saliva samples); Other: Individual electronic sensor port; Other: Atmospheric measurements of CO2
Sponsor:
Assistance Publique - Hôpitaux de Paris
Not yet recruiting
Phase I/II Study of COVID-19 DNA Vaccine (AG0302-COVID19 High-dose) - Condition: COVID-19 Lower Respiratory Infection
Interventions: Biological: AG0302-COVID19 for Intramuscular Injection; Biological: AG0302-COVID19 for Intradermal Injection
Sponsors: AnGes, Inc.; Japan Agency for Medical Research and Development
Not yet recruiting
COVID-19 Administration of Single-Dose Subcutaneous or Intramuscular Anti- Spike(s) SARS-CoV-2 Monoclonal Antibodies Casirivimab and Imdevimab in High-Risk Pediatric Participants Under 12 Years of Age - Condition: COVID-19
Intervention: Drug: casirivimab and imdevimab
Sponsor:
Regeneron Pharmaceuticals
Not yet recruiting
Reactogenicity, Safety, and Immunogenicity of Covid-19 Vaccine Booster - Condition: Covid19
Interventions: Biological: Placebo; Biological: Inactivated vaccine booster; Biological: mRNA vaccine booster; Drug: Viral vector vaccine booster
Sponsors: Universidad del Desarrollo; Ministry of Health, Chile; University of Chile; Pontificia Universidad Catolica de Chile
Active, not recruiting
Relaxation Exercise in Patients With COVID-19 - Condition: Covid19
Intervention: Other: Relaxation technique
Sponsor: Beni- Suef University
Completed
Trial of Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector, Ad5-nCoV) in Adults Living With HIV - Condition: Covid19
Intervention: Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) (Ad5-nCoV)
Sponsors: Fundación Huésped; Canadian Center for Vaccinology; CanSino Biologics Inc.; Hospital Fernandez
Recruiting
Combination of Dietary Supplements Curcumin, Quercetin and Vitamin D for Early Symptoms of COVID-19 - Condition: Covid19
Interventions: Drug: Standard of care; Dietary Supplement: combination of curcumin, quercetin and Vitamin D
Sponsor: Ayub Teaching Hospital
Not yet recruiting
Pandemic COVID-19 caused by SARS-CoV-2: genetic structure, vaccination, and therapeutic approaches - We give a summary of SARS-genetic CoV-2’s structure and evolution, as well as current attempts to develop efficient vaccine and treatment methods for SARS-CoV-2 infection, in this article. Most therapeutic strategies are based on repurposing of existing therapeutic agents used against various virus infections and focused mainly on inhibition of the virus replication cycle, enhancement of innate immunity, and alleviation of CRS caused by COVID-19. Currently, more than 100 clinical trials on…
Anti-drug antibodies to antibody-based therapeutics in multiple sclerosis - Multiple sclerosis is the major demyelinating autoimmune disease of the central nervous system. Relapsing MS can be treated by a number of approved monoclonal antibodies that currently target: CD20, CD25 (withdrawn), CD49d and CD52. These all target potentially pathogenic memory B cell subsets and perhaps functionally inhibit pathogenic T cell function. These consist of chimeric, humanized and fully human antibodies. However, despite humanization it is evident that all of these monoclonal…
Computational study for identifying promising therapeutic agents of hydroxychloroquine analogues against SARS- CoV-2 - Hydroxychloroquine (HCQ) and its derivatives have recently gained tremendous attention as a probable medicinal agent in the COVID-19 outbreak caused by SARS-CoV-2. An efficient agent to act directly in inhibiting the SARS-CoV-2 replication is yet to be achieved. Thus, the goal is to investigate the dynamic nature of HCQ derivatives against SARS-CoV-2 main protease and spike proteins. Molecular docking studies were also performed to understand their binding affinity in silico methods using the…
Combination of natural antivirals and potent immune invigorators: A natural remedy to combat COVID-19 - The flare-up in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in December 2019 in Wuhan, China, and spread expeditiously worldwide has become a health challenge globally. The rapid transmission, absence of anti-SARS-CoV-2 drugs, and inexistence of vaccine are further exacerbating the situation. Several drugs, including chloroquine, remdesivir, and favipiravir, are presently undergoing clinical investigation to further scrutinize their effectiveness and validity in the…
Zinc thiotropolone combinations as inhibitors of the SARS-CoV-2 main protease - Numerous organic molecules are known to inhibit the main protease of SARS-CoV-2, (SC2Mpro), a key component in viral replication of the 2019 novel coronavirus. We explore the hypothesis that zinc ions, long used as a medicinal supplement and known to support immune function, bind to the SC2Mpro enzyme in combination with lipophilic tropolone and thiotropolone ligands, L, block substrate docking, and inhibit function. This study combines synthetic inorganic chemistry, in vitro protease activity…
SARS-CoV-2 Spike Protein Extrapolation for COVID Diagnosis and Vaccine Development - Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to coronavirus disease 2019 (COVID-19) pandemic affecting nearly 71.2 million humans in more than 191 countries, with more than 1.6 million mortalities as of 12 December, 2020. The spike glycoprotein (S-protein), anchored onto the virus envelope, is the trimer of S-protein comprised of S1 and S2 domains which interacts with host cell receptors and facilitates virus-cell membrane fusion. The S1 domain comprises of a receptor binding…
Combination Treatment With Remdesivir and Ivermectin Exerts Highly Synergistic and Potent Antiviral Activity Against Murine Coronavirus Infection - 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…
Identification of lead compounds from large natural product library targeting 3C-like protease of SARS-CoV-2 using E-pharmacophore modelling, QSAR and molecular dynamics simulation - COVID-19 is a novel disease caused by SARS-CoV-2 and has made a catastrophic impact on the global economy. As it is, there is no officially FDA approved drug to alleviate the negative impact of SARS-CoV-2 on human health. Numerous drug targets for neutralizing coronavirus infection have been identified, among them is 3-chymotrypsin-like-protease (3CL^(pro)), a viral protease responsible for the viral replication is chosen for this study. This study aimed at finding novel inhibitors of SARS-CoV-2…
Discovery of Small Molecule Entry Inhibitors Targeting the Fusion Peptide of SARS-CoV-2 Spike Protein - SARS-CoV-2 entry into host cells relies on the spike (S) protein binding to the human ACE2 receptor. In this study, we investigated the structural dynamics of the viral S protein at the fusion peptide (FP) domain and small molecule binding for therapeutics development. Following comparative modeling analysis and docking studies of our previously identified fusion inhibitor chlorcyclizine, we performed a pharmacophore-based virtual screen and identified two novel chemotypes of entry inhibitors…
Combination of a Sindbis-SARS-CoV-2 Spike Vaccine and alphaOX40 Antibody Elicits Protective Immunity Against SARS- CoV-2 Induced Disease and Potentiates Long-Term SARS-CoV-2-Specific Humoral and T-Cell Immunity - The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 is a major global public threat. Currently, a worldwide effort has been mounted to generate billions of effective SARS-CoV-2 vaccine doses to immunize the world’s population at record speeds. However, there is still a demand for alternative effective vaccines that rapidly confer long-term protection and rely upon cost-effective, easily scaled-up manufacturing. Here, we present a Sindbis alphavirus vector (SV), transiently expressing the…
Diverse Effects of Exosomes on COVID-19: A Perspective of Progress From Transmission to Therapeutic Developments - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain of coronavirus and the causative agent of the current global pandemic of coronavirus disease 2019 (COVID-19). There are currently no FDA-approved antiviral drugs for COVID-19 and there is an urgent need to develop treatment strategies that can effectively suppress SARS-CoV-2 infection. Numerous approaches have been researched so far, with one of them being the emerging exosome-based therapies. Exosomes are nano-sized,…
Drug Design Strategies for the Treatment of Viral Disease. Plant Phenolic Compounds and Their Derivatives - The coronavirus pandemic (SARS CoV-2) that has existed for over a year, constantly forces scientists to search for drugs against this virus. In silico research and selected experimental data have shown that compounds of natural origin such as phenolic acids and flavonoids have promising antiviral potential. Phenolic compounds inhibit multiplication of viruses at various stages of the viral life cycle, e.g., attachment (disturbance of the interaction between cellular and viral receptors),…