The dynamics, duration, and nature of immunity produced during SARS-CoV-2 infection are still unclear. Here, we longitudinally measured virus-neutralising antibody, specific antibodies against the spike (S) protein, receptor-binding domain (RBD), and the nucleoprotein (N) of SARS-CoV-2, as well as T cell responses, in 25 SARS-CoV-2-infected patients up to 121 days post-symptom onset (PSO). All patients seroconvert for IgG against N, S, or RBD, as well as IgM against RBD, and produce neutralising antibodies (NAb) by 14 days PSO, with the peak levels attained by 15–30 days PSO. Anti-SARS-CoV-2 IgG and NAb remain detectable and relatively stable 3–4 months PSO, whereas IgM antibody rapidly decay. Approximately 65% of patients have detectable SARS-CoV-2-specific CD4+ or CD8+ T cell responses 3–4 months PSO. Our results thus provide critical evidence that IgG, NAb, and T cell responses persist in the majority of patients for at least 3–4 months after infection.
Seven new flavonoid glycosides (1-7), matteflavosides A-G, together with 12 known flavonoids (8-19) were isolated from the rhizomes of Matteuccia struthiopteris (L.) Todar. Their structures were established via the analyses of extensive spectroscopic data. All compounds were evaluated for their anti-influenza virus (H1N1) activity using the neuraminidase inhibition assay. The results showed that compound 7 exhibited significant inhibitory activity against the H1N1 influenza virus neuraminidase with an EC50 value of 6.8 ± 1.1 μM and an SI value of 34.4, and compounds 8 and 17 showed moderate inhibitory activity.
Cell–cell communication via
endogenous peptides and their
receptors is vital for controlling all aspects of human physiology
and most peptides signal through G protein-coupled receptors (GPCRs).
Disordered peptides bind GPCRs through complex modes for which there
are few representative crystal structures. The disordered peptide
neurotensin (NT) is a neuromodulator of classical neurotransmitters
such as dopamine and glutamate, through activation of neurotensin
receptor 1 (NTS1). While several experimental structures
show how NT binds NTS1, details about the structural dynamics
of NT during and after binding NTS1, or the role of peptide
dynamics on receptor activation, remain obscure. Here saturation transfer
difference (STD) NMR revealed that the binding mode of NT fragment
NT10-13 is heterogeneous. Epitope maps of NT10-13 at NTS1 suggested that tyrosine 11 (Y11) samples other conformations to
those observed in crystal structures of NT-bound NTS1.
Molecular dynamics (MD) simulations confirmed that when NT is bound
to NTS1, residue Y11 can exist in two χ1 rotameric states, gauche plus (g+) or gauche minus (g–). Since only the g+ Y11 state is observed
in all the structures solved to date, we asked if the g– state is important for receptor activation. NT analogues with Y11
replaced with 7-OH-Tic were synthesized to restrain the dynamics of
the side chain. P(OH-TIC)IL bound NTS1 with the same affinity
as NT10-13 but did not activate NTS1, instead acted as
an antagonist. This study highlights that flexibility of Y11 in NT
may be required for NT activation of NTS1.
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