ABSTRACT
Enveloped viruses, including human immunodeficiency virus (HIV) and SARS-CoV-2, target cells through membrane fusion process. The detailed understanding of the process is sought after for vaccine development but remains elusive due to current technique limitations for direct three-dimensional (3D) imaging of an individual virus during its viral entry. Recently, we developed a simple specimen preparation method for real-time imaging of metal dynamic liquid-vaper interface at nanometer resolution by transmission electron microscopy (TEM). Here, we extended this method to study biology sample through snapshot 3D structure of a single HIV (pseudo-typed with the envelope glycoprotein of vesicular stomatitis virus, VSV-G) at its intermediate stage of viral entry to HeLa cells in a liquid-phase environment. By individual-particle electron tomography (IPET), we found the viral surface release excess lipids with unbound viral spike proteins forming ~50-nm nanoparticles instead of merging cell membrane. Moreover, the spherical-shape shell formed by matrix proteins underneath the viral envelope does not disassemble into a cone shape right after fusion. The snapshot 3D imaging of a single virus provides us a direct structure-based understanding of the viral entry mechanism, which can be used to examine other viruses to support the development of vaccines combatting the current ongoing pandemic.
ABSTRACT
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China, and rapidly spread worldwide. This new emerging pathogen is highly transmittable and can cause fatal disease. More than 35 million cases have been confirmed and the fatality was about 2.9% up to October 9 2020. However, the original and intermediate hosts of SARS-CoV-2 remain unknown. Here, a total of 3160 poultry samples collected from 14 provinces between September and December 2019 in China were tested for the purpose of traceable surveillance for SARS-CoV-2 infection. The results indicated that all samples were SARS-CoV-2 negative, and a total of 593 avian coronaviruses were detected, including 485 avian infectious bronchitis viruses, 72 duck coronaviruses and 36 pigeon coronaviruses. The positive rates of avian infectious bronchitis virus, duck coronavirus, and pigeon coronavirus were 15.35%, 2.28% and 1.14%, respectively. Our surveillance demonstrated the diversities of avian coronaviruses in China, and higher prevalence were also recognized in some regions. The possibility of SARS-CoV-2 originating from the known avian-origin coronaviruses can be preliminarily ruled out. More surveillance and research on avian coronaviruses should be strengthened for better understanding the diversity, distribution, cross-species transmission and clinical significance of these viruses.
Subject(s)
COVID-19 , Coronavirus Infections , BronchitisABSTRACT
Background On March 11, 2020, the World Health Organization declared its assessment of COVID-19 as a global pandemic. However, specific antiviral drugs are still unavailable, and pateints are managed by multiple complementary treatments. Methods The electronic medical records of COVID-19 patients where basic information, complete blood count, coagulation profile, inflammatory cytokines and serum biochemical indicators in 42 patients with COVID-19 (21 of whom were treated with low molecular weight heparin (LMWH), and 21 without LMWH) that were retrospectively analyzed to compare and evaluate the effect of LMWH treatment on disease progression. Findings 42 patients with COVID-19 treated at the hospital between February 1 and March 15, 2020, were selected for the study, of which 21 underwent LMWH treatment (LMWH group), and 21 did not (Control), during hospitalization. Changes in the percentage of lymphocytes in the LMWH group before and after LMWH treatment were significantly different from those in the control group (p=0.011, respectively). Changes in the levels of D-dimer and fibrinogen degradation products (FDP) in the LMWH group before and after LMWH treatment were significantly different from those in the control group (p=0.002;p=0.035). Strikingly, in the LMWH group, IL-6 levels were significantly reduced after LMWH treatment (p=0.006). Besides, the changes in IL-6 levels in the LMWH group before and after LMWH treatment were significantly different from those in the control group (p=0.031). Interpretation LMWH improves the coagulation dysfunction of COVID-19 patients and exerts anti-inflammatory effects by reducing IL-6 and increasing lymphocyte %. It appears that LMWH can be used as a potential therapeutic drug for the treatment of COVID-19, paving the way for a subsequent well-controlled clinical trial. Funding National Natural Science Foundation of China (No. 81603037 to SC) and the National Key Research and Development Plan of China(2017YFC0909900).