Coronaviruses fusion with the membrane and entry to the host cell

Abstract

Introduction. Coronaviruses (CoVs) are positive-strand RNA viruses with the largest genome among all RNA viruses. They are able to infect many host, such as mammals or birds. Whereas CoVs were identified 1930s, they became known again in 2003 as the agents of the Severe Acute Respiratory Syndrome (SARS). The spike protein is thought to be essential in the process of CoVs entry, because it is associated with the binding to the receptor on the host cell. It is also involved in cell tropism and pathogenesis. Receptor recognition is the crucial step in the infection. CoVs are able to bind a variety of receptors, although the selection of receptor remains unclear. Coronaviruses were initially believed to enter cells by fusion with the plasma membrane. Further studies demonstrated that many of them involve endocytosis through clathrin-dependent, caveolae-dependent, clathrin-independent, as well as caveolae-independent mechanisms. Objectives. The aim of this review is to summarise current knowledge about coronaviruses, focussing especially on CoVs entry into the host cell. Advances in understanding coronaviruses replication strategy and the functioning of the replicative structures are also highlighted. The development of host-directed antiviral therapy seems to be a promising way to treat infections with SARS-CoV or other pathogenic coronaviruses. There is still much to be discovered in the inventory of proand anti-viral host factors relevant for CoVs replication. The latest pandemic danger, originating from China, has given our previously prepared work even more of topicality.

Repurposing Sigma-1 Receptor Ligands for COVID-19 Therapy?

“…Binding of the spike (S) protein of SARS-CoV-2 to its receptor exposes its cleavage sites to cellular proteases, including endosomal acid proteases involved in endocytic processing (Millet and Whittaker, 2015;Pillay, 2020). In particular, endosomal cathepsin-mediated S protein cleavage is considered a critical step for CoV entry and initiation of infection (Millet and Whittaker, 2015;Glebov, 2020;Wędrowska et al, 2020;Yang and Shen, 2020).…”

“…Endosomes and maturation of endosomes into a lysosome is featured by their acidic internal pH, which is required for acid proteases and critical for SARS-CoV-2 processing and internalization (Wędrowska et al, 2020). The plasma and lysosomal membranes are highly permeable to the unionized form of weak bases but are essentially impervious to the protonated form of the bases (Marceau et al, 2012;Homolak and Kodvanj, 2020).…”

Molecular basis of COVID-19 pathogenesis and in silico studies of potential pharmacological treatment

“…La subunidad S1 presenta un dominio N-terminal, un dominio C-terminal (51) y un dominio de unión al receptor conservado (RBD) que contiene un núcleo y un motivo de unión al receptor (RBM) (51) . Esta subunidad media la unión al receptor ECA 2, donde los residuos de aminoácidos como Lys317 y Phe486 del dominio RBD podrían ser claves para esta interacción (51,52) .…”

“…Por otro lado, la sub unidad S2 posee en su estructura un dominio péptido de fusión (FP), dominios de repetición heptad-1 y -2 (HR1, HR2) y un dominio transmembrana (TM), que le permiten la fusión de las membranas viral y celular (51,52) .…”

The Novel Insight of SARS-CoV-2 Molecular Biology and Pathogenesis and Therapeutic Options

“…Virus membrane fused with host membrane resulted in SARS-CoV-2 entering the host cell as enodocytosis through clathrin-dependent or clathrin-independent ways (Wędrowska et al, 2020;Algarroba et al, 2020). Then, the viral genome is released into the cytosolic space via lysosomal enzymes that are referred to as catapsin L and trypsin (Hoffmann et al, 2020a).…”