Approaching Protein Aggregation and Structural Dynamics by Equilibrium and Nonequilibrium Paramagnetic Perturbation.

PENELOP (Paramagnetic Equilibrium vs Nonequilibrium magnetization Enhancement or LOss Perturbation) is the presented nuclear magnetic resonance (NMR) approach to identify at once the location of proteins' exposed surface, hindered accessibility, and exchange processes occurring on a µs-ms time scale. In addition to mapping the protein surface accessibility, the application of this method under specific conditions makes it possible to distinguish conformational mobility and chemical exchange processes, thereby providing an alternative to characterization by more demanding techniques (transverse relaxation dispersion, saturation transfer, and high-pressure NMR). Moreover, its high sensitivity enables studying samples at low, physiologically more relevant concentrations. Association, dynamics, and oligomerization are addressed by PENELOP for a component of SARS-CoV-2 replication transcription complex and an amyloidogenic protein.

An Overview on the Potential Roles of EGCG in the Treatment of COVID-19 Infection.

Coronavirus disease-19 (COVID-19) pandemic is currently ongoing worldwide and causes a lot of deaths in many countries. Although different vaccines for the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection have been developed and are now available, there are no effective antiviral drugs to treat the disease, except for Remdesivir authorized by the US FDA to counteract the emergency. Thus, it can be useful to find alternative therapies based on the employment of natural compounds, with antiviral features, to circumvent SARS-CoV-2 infection. Pre-clinical studies highlighted the antiviral activities of epigallocatechin-3-gallate (EGCG), a catechin primarily found in green tea, against various viruses, including SARS-CoV-2. In this review, we summarize this experimental evidence and highlight the potential use of EGCG as an alternative therapeutic choice for the treatment of SARS-CoV-2 infection.

NMR-Based Analysis of Nanobodies to SARS-CoV-2 Nsp9 Reveals a Possible Antiviral Strategy Against COVID-19.

Following the entry into the host cell, SARS-CoV-2 replication is mediated by the replication transcription complex (RTC) assembled through a number of nonstructural proteins (Nsps). A monomeric form of Nsp9 is particularly important for RTC assembly and function. In the present study, 136 unique nanobodies targeting Nsp9 are generated. Several nanobodies belonging to different B-cell lineages are expressed, purified, and characterized. Results from immunoassays applied to purified Nsp9 and neat saliva from coronavirus disease (COVID-19) patients show that these nanobodies effectively and specifically recognize both recombinant and endogenous Nsp9. Nuclear magnetic resonance analyses supported by molecular dynamics reveal a composite Nsp9 oligomerization pattern and demonstrate that both nanobodies stabilize the tetrameric form of wild-type Nsp9 also identifying the epitopes on the tetrameric assembly. These results can have important implications in the potential use of these nanobodies to combat viral replication.

COVID-19 Vaccine mRNABNT162b2 Elicits Human Antibody Response in Milk of Breastfeeding Women.

OBJECTIVE: The objective of this research is to demonstrate the release of SARS-CoV-2 Spike (S) antibodies in human milk samples obtained by patients who have been vaccinated with mRNABNT162b2 vaccine. METHODS: Milk and serum samples were collected in 10 volunteers 20 days after the first dose and 7 seven days after the second dose of the mRNABNT162b2 vaccine. Anti-SARS-CoV-2 S antibodies were measured by the Elecsys® Anti-SARS-CoV-2 S ECLIA assay (Roche Diagnostics AG, Rotkreuz, Switzerland), a quantitative electrochemiluminescence immunometric method. RESULTS: At first sample, anti-SARS-CoV-2 S antibodies were detected in all serum samples (103.9 ± 54.9 U/mL) and only in two (40%) milk samples with a low concentration (1.2 ± 0.3 U/mL). At the second sample, collected 7 days after the second dose, anti-SARS-CoV-2 S antibodies were detected in all serum samples (3875.7 ± 3504.6 UI/mL) and in all milk samples (41.5 ± 47.5 UI/mL). No correlation was found between the level of serum and milk antibodies; the milk antibodies/serum antibodies ratio was on average 2% (range: 0.2-8.4%). CONCLUSION: We demonstrated a release of anti-SARS-CoV-2 S antibodies in the breast milk of women vaccinated with mRNABNT162b2. Vaccinating breastfeeding women could be a strategy to protect their infants from COVID-19 infection.