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2.
Struct Chem ; 31(6): 2391-2412, 2020.
Article in English | MEDLINE | ID: covidwho-1906457

ABSTRACT

Presently, the SARS-CoV-2 (COVID-19) pandemic has been spreading throughout the world. Some drugs such as lopinavir, simeprevir, hydroxychloroquine, chloroquine, and amprenavir have been recommended for COVID-19 treatment by some researchers, but these drugs were not effective enough against this virus. This study based on in silico approaches was aimed to increase the anti-COVID-19 activities of these drugs by using caulerpin and its derivatives as an adjunct drug against SARS-CoV-2 receptor proteins: the SARS-CoV-2 main protease and the SARS-CoV-2 spike protein. Caulerpin exhibited antiviral activities against chikungunya virus and herpes simplex virus type 1. Caulerpin and some of its derivatives showed inhibitory activity against Alzheimer's disease. The web server ANCHOR revealed higher protein stability for the two receptors with disordered score (< 0.6). Molecular docking analysis showed that the binding energies of most of the caulerpin derivatives were higher than all the suggested drugs for the two receptors. Also, we deduced that inserting NH2, halogen, and vinyl groups can increase the binding affinity of caulerpin toward 6VYB and 6LU7, while inserting an alkyl group decreases the binding affinity of caulerpin toward 6VYB and 6LU7. So, we can modify the inhibitory effect of caulerpin against 6VYB and 6LU7 by inserting NH2, halogen, and vinyl groups. Based on the protein disordered results, the SARS-CoV-2 main protease and SARS-CoV-2 spike protein domain are highly stable proteins, so it is quite difficult to unstabilize their integrity by using individual drugs. Also, molecular dynamics (MD) simulation indicates that binding of the combination therapy of simeprevir and the candidate studied compounds to the receptors was stable and had no major effect on the flexibility of the protein throughout the simulations and provided a suitable basis for our study. So, this study suggested that caulerpin and its derivatives could be used as a combination therapy along with lopinavir, simeprevir, hydroxychloroquine, chloroquine, and amprenavir for disrupting the stability of SARS-CoV2 receptor proteins to increase the antiviral activity of these drugs.

3.
PLoS One ; 16(4): e0250853, 2021.
Article in English | MEDLINE | ID: covidwho-1833535

ABSTRACT

BACKGROUND: Infection by SARS-CoV-2 in domestic animals has been related to close contact with humans diagnosed with COVID-19. Objectives: To assess the exposure, infection, and persistence by SARS-CoV-2 of dogs and cats living in the same households of humans that tested positive for SARS-CoV-2, and to investigate clinical and laboratory alterations associated with animal infection. METHODS: Animals living with COVID-19 patients were longitudinally followed and had nasopharyngeal/oropharyngeal and rectal swabs collected and tested for SARS-CoV-2. Additionally, blood samples were collected for laboratory analysis, and plaque reduction neutralization test (PRNT90) to investigate specific SARS-CoV-2 antibodies. RESULTS: Between May and October 2020, 39 pets (29 dogs and 10 cats) of 21 patients were investigated. Nine dogs (31%) and four cats (40%) from 10 (47.6%) households were infected with or seropositive for SARS-CoV-2. Animals tested positive from 11 to 51 days after the human index COVID-19 case onset of symptoms. Three dogs tested positive twice within 14, 30, and 31 days apart. SARS-CoV-2 neutralizing antibodies were detected in one dog (3.4%) and two cats (20%). In this study, six out of thirteen animals either infected with or seropositive for SARS-CoV-2 have developed mild but reversible signs of the disease. Using logistic regression analysis, neutering, and sharing bed with the ill owner were associated with pet infection. CONCLUSIONS: The presence and persistence of SARS-CoV-2 infection have been identified in dogs and cats from households with human COVID-19 cases in Rio de Janeiro, Brazil. People with COVID-19 should avoid close contact with their pets during the time of their illness.


Subject(s)
COVID-19/epidemiology , COVID-19/veterinary , Pets/virology , Animals , Animals, Domestic/virology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Brazil/epidemiology , Cat Diseases , Cats , Dog Diseases , Dogs , Longitudinal Studies , Prevalence , SARS-CoV-2/pathogenicity
4.
J Infect Dis ; 2021 Mar 16.
Article in English | MEDLINE | ID: covidwho-1706826

ABSTRACT

Immunoglobulin (IG) lots (N=176) released since March 2020 were tested for SARS-CoV-2 neutralizing antibodies, with first positive results for September 2020 lots, mean = 1.7 IU/ml, 46% of lots positive. From there, values steadily increased, in correlation with the cumulative COVID-19 incidence, to reach a mean of 31.2 IU/ml and 93% of lots positive by January 2021. Extrapolating the correlation, IGs could reach an anti-SARS-CoV-2 potency of ~345 IU/ml by July 2021. At that stage, prophylactic IG treatment for primary/secondary immunodeficiency could contain similar doses of anti-SARS-CoV-2 as convalescent plasma which is used for treatment of COVID-19.

5.
Biophys J ; 120(14): 2828-2837, 2021 07 20.
Article in English | MEDLINE | ID: covidwho-1606137

ABSTRACT

The cell surface receptor Neuropilin-1 (Nrp1) was recently identified as a host factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry. The Spike protein of SARS-CoV-2 is cleaved into two segments, the S1 (residues (res.) 1-685) and the S2 (res. 686-1273) domains by furin protease. Nrp1 predominantly binds to the C-terminal RRAR amino acid motif (res. 682-685) of the S1 domain. In this study, we firstly modeled the association of an Nrp1 protein (consisting of domains a2-b1-b2) with the Spike protein. Next, we studied the separation of S2 from the S1 domain, with and without Nrp1 bound, by utilizing molecular dynamics pulling simulations. During the separation, Nrp1 stabilizes the S1 C-terminal region (res. 640-685) and thereby assists the detachment of S2 N-terminal region (res. 686-700). Without Nrp1 bound, S1 tends to become stretched, whereas the bound Nrp1 stimulates an earlier separation of S2 from the S1 domain. The liberated S2 domain is known to mediate the fusion of virus and host membranes; thus, Nrp1 likely increases virus infectivity by facilitating the S1 and S2 separation. We further analyzed the possible topological structure of the SARS-CoV-2 Spike protein when bound with Nrp1 and angiotensin-converting enzyme 2 (ACE2). Understanding of such an Nrp1-assisted viral infection opens the gate for the generation of protein-protein inhibitors, such as antibodies, which could attenuate the infection mechanism and protect certain cells in a future Nrp1-ACE2 targeted combination therapy.

6.
Clin Infect Dis ; 73(12): 2155-2162, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1592795

ABSTRACT

BACKGROUND: Assessing the duration of immunity following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a first priority to gauge the degree of protection following infection. Such knowledge is lacking, especially in the general population. Here, we studied changes in immunoglobulin isotype seropositivity and immunoglobulin G (IgG) binding strength of SARS-CoV-2-specific serum antibodies up to 7 months following onset of symptoms in a nationwide sample. METHODS: Participants from a prospective representative serological study in the Netherlands were included based on IgG seroconversion to the spike S1 protein of SARS-CoV-2 (N = 353), with up to 3 consecutive serum samples per seroconverted participant (N = 738). Immunoglobulin M (IgM), immunoglobulin A (IgA), and IgG antibody concentrations to S1, and increase in IgG avidity in relation to time since onset of disease symptoms, were determined. RESULTS: While SARS-CoV-2-specific IgM and IgA antibodies declined rapidly after the first month after disease onset, specific IgG was still present in 92% (95% confidence interval [CI], 89%-95%) of the participants after 7 months. The estimated 2-fold decrease of IgG antibodies was 158 days (95% CI, 136-189 days). Concentrations were sustained better in persons reporting significant symptoms compared to asymptomatic persons or those with mild upper respiratory complaints only. Similarly, avidity of IgG antibodies for symptomatic persons showed a steeper increase over time compared with persons with mild or no symptoms (P = .022). CONCLUSIONS: SARS-CoV-2-specific IgG antibodies persist and show increasing avidity over time, indicative of underlying immune maturation. These data support development of immune memory against SARS-CoV-2, providing insight into protection of the general unvaccinated part of the population. CLINICAL TRIALS REGISTRATION: NL8473 (the Dutch trial registry).


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Netherlands/epidemiology , Prospective Studies
7.
Vox Sang ; 116(10): 1076-1083, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1515248

ABSTRACT

BACKGROUND AND OBJECTIVES: Convalescent plasma (CP) has been embraced as a safe therapeutic option for coronavirus disease 2019 (COVID-19), while other treatments are developed. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not transmissible by transfusion, but bloodborne pathogens remain a risk in regions with high endemic prevalence of disease. Pathogen reduction can mitigate this risk; thus, the objective of this study was to evaluate the effect of riboflavin and ultraviolet light (R + UV) pathogen reduction technology on the functional properties of COVID-19 CP (CCP). MATERIALS AND METHODS: COVID-19 convalescent plasma units (n = 6) from recovered COVID-19 research donors were treated with R + UV. Pre- and post-treatment samples were tested for coagulation factor and immunoglobulin retention. Antibody binding to spike protein receptor-binding domain (RBD), S1 and S2 epitopes of SARS-CoV-2 was assessed by ELISA. Neutralizing antibody (nAb) function was assessed by pseudovirus reporter viral particle neutralization (RVPN) assay and plaque reduction neutralization test (PRNT). RESULTS: Mean retention of coagulation factors was ≥70%, while retention of immunoglobulins was 100%. Starting nAb titres were low, but PRNT50 titres did not differ between pre- and post-treatment samples. No statistically significant differences were detected in levels of IgG (P ≥ 0·3665) and IgM (P ≥ 0·1208) antibodies to RBD, S1 and S2 proteins before and after treatment. CONCLUSION: R + UV PRT effects on coagulation factors were similar to previous reports, but no significant effects were observed on immunoglobulin concentration and antibody function. SARS-CoV-2 nAb function in CCP is conserved following R + UV PRT treatment.


Subject(s)
Antibodies, Neutralizing , COVID-19 , Antibodies, Viral , COVID-19/therapy , Humans , Immunization, Passive , Riboflavin , SARS-CoV-2 , Technology , Ultraviolet Rays
9.
Antimicrob Agents Chemother ; 65(8): e0035021, 2021 07 16.
Article in English | MEDLINE | ID: covidwho-1486470

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread rapidly worldwide. This study is the first to report the tolerability, safety, pharmacokinetics (PK), and immunogenicity of a recombinant human anti-SARS-CoV-2 monoclonal antibody, etesevimab (CB6, JS016, LY3832479, or LY-CoV016), in healthy adults. This paper describes a randomized, double-blind, placebo-controlled, phase 1 study. A total of 40 participants were enrolled to receive a single intravenous dose of either etesevimab or placebo in one of four sequential ascending intravenous dose cohorts. All 40 participants completed the study. Seventeen (42.5%) participants experienced 22 treatment emergent adverse events (TEAEs) that were drug-related, and the rates of these TEAEs among different dose cohorts were numerically comparable. No difference was observed between the combined etesevimab group and the placebo group. The exposure after etesevimab infusion increased in an approximately proportional manner as the dose increased from 2.5 to 50 mg/kg. The elimination half-life (t1/2) value did not differ among different dose cohorts and was estimated to be around 4 weeks. Etesevimab was well tolerated after administration of a single dose at a range of 2.5 mg/kg to 50 mg/kg in healthy Chinese adults. The PK profiles of etesevimab in healthy volunteers showed typical monoclonal antibody distribution and elimination characteristics. (This study has been registered at ClinicalTrials.gov under identifier NCT04441918.).


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Antibodies, Neutralizing , Antibodies, Viral , China , Double-Blind Method , Humans
10.
Crit Care Med ; 49(10): 1749-1756, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1475873

ABSTRACT

OBJECTIVES: Nonpharmaceutical interventions are implemented internationally to mitigate the spread of severe acute respiratory syndrome coronavirus 2 with the aim to reduce coronavirus disease 2019-related deaths and to protect the health system, particularly intensive care facilities from being overwhelmed. The aim of this study is to describe the impact of nonpharmaceutical interventions on ICU admissions of non-coronavirus disease 2019-related patients. DESIGN: Retrospective cohort study. SETTING: Analysis of all reported adult patient admissions to New Zealand ICUs during Level 3 and Level 4 lockdown restrictions from March 23, to May 13, 2020, in comparison with equivalent periods from 5 previous years (2015-2019). SUBJECTS: Twelve-thousand one-hundred ninety-two ICU admissions during the time periods of interest were identified. MEASUREMENTS: Patient data were obtained from the Australian and New Zealand Intensive Care Society Adult Patient Database, Australian and New Zealand Intensive Care Society critical care resources registry, and Statistics New Zealand. Study variables included patient baseline characteristics and ICU resource use. MAIN RESULTS: Nonpharmaceutical interventions in New Zealand were associated with a 39.1% decrease in ICU admission rates (p < 0.0001). Both elective (-44.2%) and acute (-36.5%) ICU admissions were significantly reduced when compared with the average of the previous 5 years (both p < 0.0001). ICU occupancy decreased from a mean of 64.3% (2015-2019) to 39.8% in 2020. Case mix, ICU resource use per patient, and ICU and hospital mortality remained unchanged. CONCLUSIONS: The institution of nonpharmaceutical interventions was associated with a significant decrease in elective and acute ICU admissions and ICU resource use. These findings may help hospitals and health authorities planning for surge capacities and elective surgery management in future pandemics.


Subject(s)
COVID-19/diagnosis , Hospitalization/statistics & numerical data , Intensive Care Units/statistics & numerical data , Quarantine/statistics & numerical data , Adult , Aged , COVID-19/epidemiology , Cohort Studies , Female , Humans , Intensive Care Units/organization & administration , Male , Middle Aged , New Zealand/epidemiology , Retrospective Studies
11.
Curr Pharm Des ; 27(32): 3476-3489, 2021.
Article in English | MEDLINE | ID: covidwho-1470720

ABSTRACT

BACKGROUND: The main proteases (Mpro) and Spike Proteins (SP) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) play a major role in viral infection development by producing several non-structural proteins (nsPs) and penetrating the host cells, respectively. In this study, the potential of in silico molecular docking-based drug repositioning approach was exploited for identifying the inhibitors of Mpro and SP of SARS-CoV-2. METHODS: A total of 196 compounds, including various US-FDA-approved drugs, vitamins, and their analogs, were docked with Mpro (PDB IDs: 6YB7 and 6Y84), and the top six ligands were further tested for ADME properties, followed by docking with SP (PDB IDs: 6LXT and 6W41). RESULTS: Out of 196 compounds, binding energy (DE) of Silybin B (6YB7: DE: -11.20 kcal/mol; 6Y84: DE: - 10.18 kcal/mol; 6LXT: DE: -10.47 kcal/mol; 6W41: DE: -10.96 kcal/mol) and Cianidanol (6YB7: DE: -8.85 kcal/mol; 6LXT: DE: -9.36 kcal/mol; 6Y84: DE: -10.02 kcal/mol; 6W41: DE: -9.52 kcal/mol) demonstrated better binding and ADME properties compared with the currently endeavored drugs like Hydroxychloroquine and Lopinavir. Additionally, Elliptinone, Diospyirin, SCHEMBL94263, and Fiboflavin have shown encouraging results. Fiboflavin, an immunity booster, was found to inhibit both the Mpro and spike protein of SARSCoV- 2. It was observed that amino acid residues MET6, ALA7, PHE8, PRO9, ASP295, GLY302, VAL303, and THR304 play significant roles in protein-ligand interactions through hydrogen bonds and Vander Waals forces. CONCLUSION: Silybin B and Cianidanol showed excellent binding and ADME properties compared with the currently endeavored drugs and can be exploited as therapeutic options against SARS-CoV-2 infection after experimental validation and clinical trials.


Subject(s)
COVID-19 , Catechin , Antiviral Agents/pharmacology , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , SARS-CoV-2 , Silybin , Spike Glycoprotein, Coronavirus
12.
Perfusion ; 36(8): 798-802, 2021 11.
Article in English | MEDLINE | ID: covidwho-1455838

ABSTRACT

AIM: Patients with cardiogenic shock or ARDS, for example, in COVID-19/SARS-CoV-2, may require extracorporeal membrane oxygenation (ECMO). An ECLS/ECMO model simulating challenging vascular anatomy is desirable for cannula insertion training purposes. We assessed the ability of various 3D-printable materials to mimic the penetration properties of human tissue by using porcine aortae. METHODS: A test bench for needle penetration and piercing in sampled porcine aorta and preselected 3D-printable polymers was assembled. The 3D-printable materials had Shore A hardness of 10, 20, and 50. 17G Vygon 1.0 × 1.4 mm × 70 mm needles were used for penetration tests. RESULTS: For the porcine tissue and Shore A 10, Shore A 20, and Shore A 50 polymers, penetration forces of 0.9036 N, 0.9725 N, 1.0386 N, and 1.254 N were needed, respectively. For piercing through the porcine tissue and Shore A 10, Shore A 20, and Shore A 50 polymers, forces of 0.8399 N, 1.244 N, 1.475 N, and 1.482 N were needed, respectively. ANOVA showed different variances among the groups, and pairwise two-tailed t-tests showed significantly different needle penetration and piercing forces, except for penetration of Shore A 10 and 20 polymers (p = 0.234 and p = 0.0857). Significantly higher forces were required for all other materials. CONCLUSION: Shore A 10 and 20 polymers have similar needle penetration properties compared to the porcine tissue. Significantly more force is needed to pierce through the material fully. The most similar tested material to porcine aorta for needle penetration and piercing in ECMO-implantation is the silicon Shore A 10 polymer. This silicon could be a 3D-printable material in surgical training for ECMO-implantation.


Subject(s)
COVID-19 , Extracorporeal Membrane Oxygenation , Animals , Aorta , Humans , Needles , SARS-CoV-2 , Shock, Cardiogenic , Swine
13.
Clin J Am Soc Nephrol ; 16(7): 1073-1082, 2021 07.
Article in English | MEDLINE | ID: covidwho-1444004

ABSTRACT

BACKGROUND AND OBJECTIVES: Patients receiving hemodialysis are at high risk for both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe coronavirus disease 2019. A lifesaving vaccine is available, but sensitivity to vaccines is generally lower in patients on dialysis. Little is yet known about antibody responses after coronavirus disease 2019 (COVID-19) vaccination in this vulnerable group. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: In this prospective single-center study, we included 22 patients on dialysis and 46 healthy controls from Heidelberg University Hospital between December 2020 and February 2021. We measured anti-S1 IgG with a threshold index for detection greater than one, neutralizing antibodies with a threshold for viral neutralization of ≥30%, and antibodies against different SARS-CoV2 fragments 17-22 days after the first dose and 18-22 days after the second dose of the mRNA vaccine BNT162b2. RESULTS: After the first vaccine dose, four of 22 (18%) patients on dialysis compared with 43 of 46 (93%) healthy controls developed positive anti-S1 IgG, with a median anti-S1 IgG index of 0.2 (interquartile range, 0.1-0.7) compared with nine (interquartile range, 4-16), respectively. SARS-CoV2 neutralizing antibodies exceeded the threshold for neutralization in four of 22 (18%) patients on dialysis compared with 43 of 46 (93%) healthy controls, with a median percent inhibition of 11 (interquartile range, 3-24) compared with 65 (interquartile range, 49-75), respectively. After the second dose, 14 of 17 (82%) patients on dialysis developed neutralizing antibodies exceeding the threshold for viral neutralization and antibodies against the receptor binding S1 domain of the spike protein, compared with 46 of 46 (100%) healthy controls, respectively. The median percent inhibition was 51 (interquartile range, 32-86) compared with 98 (interquartile range, 97-98) in healthy controls. CONCLUSIONS: Patients receiving long-term hemodialysis show a reduced antibody response to the first and second doses of the mRNA vaccine BNT162b2. The majority (82%) develop neutralizing antibodies after the second dose but at lower levels than healthy controls.


Subject(s)
Antibodies, Viral/blood , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Renal Dialysis , SARS-CoV-2/immunology , Vaccination , Adult , Age Factors , Aged , Aged, 80 and over , BNT162 Vaccine , Female , Humans , Immunoglobulin G/blood , Male , Middle Aged
14.
J Infect Dis ; 224(6): 956-966, 2021 09 17.
Article in English | MEDLINE | ID: covidwho-1429243

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to be a major public health challenge globally. The identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-derived T-cell epitopes is of critical importance for peptide vaccines or diagnostic tools of COVID-19. METHODS: In this study, several SARS-CoV-2-derived human leukocyte antigen (HLA)-I binding peptides were predicted by NetMHCpan-4.1 and selected by Popcover to achieve pancoverage of the Chinese population. The top 5 ranked peptides derived from each protein of SARS-CoV-2 were then evaluated using peripheral blood mononuclear cells from unexposed individuals (negative for SARS-CoV-2 immunoglobulin G). RESULTS: Seven epitopes derived from 4 SARS-CoV-2 proteins were identified. It is interesting to note that most (5 of 7) of the SARS-CoV-2-derived peptides with predicted affinities for HLA-I molecules were identified as HLA-II-restricted epitopes and induced CD4+ T cell-dependent responses. These results complete missing pieces of pre-existing SARS-CoV-2-specific T cells and suggest that pre-existing T cells targeting all SARS-CoV-2-encoded proteins can be discovered in unexposed populations. CONCLUSIONS: In summary, in the current study, we present an alternative and effective strategy for the identification of T-cell epitopes of SARS-CoV-2 in healthy subjects, which may indicate an important role in the development of peptide vaccines for COVID-19.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , COVID-19/prevention & control , Epitopes, T-Lymphocyte/immunology , Vaccines, Subunit/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cell Line , Humans , Leukocytes, Mononuclear/immunology , SARS-CoV-2
16.
Struct Chem ; 32(5): 1985-1992, 2021.
Article in English | MEDLINE | ID: covidwho-1384542

ABSTRACT

In this study, we have investigated the binding mechanism of two FDA-approved drugs (ivermectin and levosalbutamol) with the spike protein of SARs-CoV-2 using three different computational modeling techniques. Molecular docking results predict that ivermectin shows a large binding affinity for spike protein (- 9.0 kcal/mol) compared to levosalbutamol (- 4.1 kcal/mol). Ivermectin binds with LEU492, GLN493, GLY496, and TRY505 residues in the spike protein through hydrogen bonds and levosalbutamol binds with TYR453 and TYR505 residues. Using density functional theory (DFT) studies, we have calculated the binding energies between ivermectin and levosalbutamol with residues in spike protein which favor their binding are - 22.4 kcal/mol and - 21.08 kcal/mol, respectively. The natural bond orbital (NBO) charge analysis has been performed to estimate the amount of charge transfer that occurred by two drugs during interaction with residues. Molecular dynamics (MD) study confirms the stability of spike protein bound with ivermectin through RMSD and RMSF analyses. Three different computer modeling techniques reveal that ivermectin is more stable than levosalbutamol in the active site of spike protein where hACE2 binds. Therefore, ivermectin can be a suitable inhibitor for SARS-CoV-2 to enter into the human cell through hACE2.

18.
Front Mol Biosci ; 8: 658687, 2021.
Article in English | MEDLINE | ID: covidwho-1389215

ABSTRACT

Many current strategies for inducing an immune response rely on the production of an antigenic protein. Such methods can be problematic if the folding of the antigenic protein is incorrect. To avoid this problem, we propose a method based on grafting specific regions of the chosen antigenic protein onto biocompatible polymeric matrices, so that they can mimic portions of the antigenic protein. These regions are selected following the criterion according to which they are not folded, are exposed to the solvent and are not already present in the human body, so that they are not recognized by the immune system as self. Regions are selected using the primary sequence of the protein and, where possible, its tertiary structure. The application of this strategy to the Spike protein of SARS-CoV-2 is presented.

19.
Front Med (Lausanne) ; 8: 672629, 2021.
Article in English | MEDLINE | ID: covidwho-1389198

ABSTRACT

SARS-CoV-2 infection across the world has led to immense turbulence in the treatment modality, thus demanding a swift drug discovery process. Spike protein of SARS-CoV-2 binds to ACE2 receptor of human to initiate host invasion. Plethora of studies demonstrate the inhibition of Spike-ACE2 interactions to impair infection. The ancient Indian traditional medicine has been of great interest of Virologists worldwide to decipher potential antivirals. Hence, in this study, phytochemicals (1,952 compounds) from eight potential medicinal plants used in Indian traditional medicine were meticulously collated, based on their usage in respiratory disorders, along with immunomodulatory and anti-viral potential from contemporary literature. Further, these compounds were virtually screened against Receptor Binding Domain (RBD) of Spike protein. The potential compounds from each plant were prioritized based on the binding affinity, key hotspot interactions at ACE2 binding region and glycosylation sites. Finally, the potential hits in complex with spike protein were subjected to Molecular Dynamics simulation (450 ns), to infer the stability of complex formation. Among the compounds screened, Tellimagrandin-II (binding energy of -8.2 kcal/mol and binding free energy of -32.08 kcal/mol) from Syzygium aromaticum L. and O-Demethyl-demethoxy-curcumin (binding energy of -8.0 kcal/mol and binding free energy of -12.48 kcal/mol) from Curcuma longa L. were found to be highly potential due to their higher binding affinity and significant binding free energy (MM-PBSA), along with favorable ADMET properties and stable intermolecular interactions with hotspots (including the ASN343 glycosylation site). The proposed hits are highly promising, as these are resultant of stringent in silico checkpoints, traditionally used, and are documented through contemporary literature. Hence, could serve as promising leads for subsequent experimental validations.

20.
Emerg Infect Dis ; 27(2): 663-666, 2021 02.
Article in English | MEDLINE | ID: covidwho-1389113

ABSTRACT

Antibody response against nucleocapsid and spike proteins of SARS-CoV-2 in 11 persons with mild or asymptomatic infection rapidly increased after infection. At weeks 18-30 after diagnosis, all remained seropositive but spike protein-targeting antibody titers declined. These data may be useful for vaccine development.


Subject(s)
COVID-19/immunology , Immunity, Humoral , SARS-CoV-2/immunology , Adolescent , Adult , Antibodies, Viral/blood , Antibodies, Viral/immunology , Asymptomatic Infections , COVID-19/blood , COVID-19/virology , Child , Female , Humans , Longitudinal Studies , Male , Middle Aged , Nucleocapsid Proteins/blood , Nucleocapsid Proteins/immunology , Spike Glycoprotein, Coronavirus/blood , Spike Glycoprotein, Coronavirus/immunology , Time Factors , Vietnam , Young Adult
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