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Nanomedicine Against COVID-19
Published in Hanadi Talal Ahmedah, Muhammad Riaz, Sagheer Ahmed, Marius Alexandru Moga, The Covid-19 Pandemic, 2023
Saima Zulfiqar, Zunaira Naeem, Shahzad Sharif, Ayoub Rashid Ch., M. Zia-Ul-Haq, Marius Moga
These produced polyproteins generate 15 to 16 non-structural proteins via autoproteolytic cleavage. These nonstructural proteins are responsible for some significant activities like: nsp12 can encode the RNA-polymerase activity which is RNA-dependent [23];nsp3, nsp4, and nsp6 through spherules or DMV (double-membrane vesicle) can mediate the rearrangement of cell-membrane;nsp3 and nsp5 can encode the protease-PLpro just like papain [37] and major activities of protease-Mpro sequentially [38, 39].
The Viruses
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Viruses may produce “nonstructural” proteins in addition to structural ones. These are usually enzymes involved in the replication of the virus particle. These proteins may include transcriptases or enzymes that recognize templates normally utilized by the cell such as RNA-dependent RNA polymerases and “reverse transcriptase” which is used by retroviruses to produce a DNA intermediate from an RNA template. The demonstration of virus-associated enzymatic activity is a method for detection of the presence of viruses in cells.
AI and Immunology Considerations in Pandemics and SARS-CoV-2 COVID-19
Published in Louis J. Catania, AI for Immunology, 2021
Vaxign (see also Vaccines, page 110) is a reverse vaccinology tool being used with Vaxign-ML machine learning tool to predict COVID-19 vaccine candidates. A study applied the state-of-the-art Vaxign reserve vaccinology (RV) and Vaxign-ML machine learning strategies to the entire SARS-CoV-2 proteomes including both structural and non-structural proteins for vaccine candidate prediction. The results indicate for the first time that many non-structural proteins could be used as potential vaccine candidates.32
Diagnostic approaches for dengue infection
Published in Expert Review of Molecular Diagnostics, 2023
Gaythri Thergarajan, Shamala Devi Sekaran
DENV is a single-stranded positive-sense RNA virus of approximately 50 nm in length. The 11 kb genome of each virion encodes three structural proteins (capsid, C; precursor membrane, prM; and envelope, E) and seven non-structural (NS) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) [60]. These non-structural proteins play roles in viral replication and assembly. Structurally, a virion consists of a nucleocapsid, enveloped by an outer glycoprotein shell and an inner lipid bilayer. Surface projections in the lipid membrane consist of E and membrane (M) glycoproteins [61]. Nucleic acid amplification tests and identification of virus antigen or antibody serve as the predominant means of detection of DENV, based on the molecular or immunological response to specified viral structural components. Commonly used methods are reverse transcription polymerase chain reaction (RT-PCR), nucleic acid sequence-based amplification (NASBA), and transcription-mediated amplification (TMA).
An overview of the recent progress in Middle East Respiratory Syndrome Coronavirus (MERS-CoV) drug discovery
Published in Expert Opinion on Drug Discovery, 2023
MERS-CoV remains a public health concern despite the fact that it emerged more than a decade ago. Several methods of drug discovery have been adopted to generate MERS-CoV inhibitors by targeting both viral and host cell molecular sites. Viral protein targets comprised both structural and nonstructural proteins. MERS-CoV inhibitors can be best described by their actions. Attachment and entry, endocytotic, fusion, and replication inhibitors have all been developed for use against MERS-CoV. Compounds with strong antiviral actions were discovered with potency in the lower micromolar range and the nanomolar range. These compounds can be further investigated by chemical modifications to deliver more potent drug candidates. Clinical trials in the application of new MERS-CoV inhibitors are very few. The adoption of strong MERS-CoV inhibitors in clinical phases is highly recommended.
Analysis of the SARS-CoV-2-host protein interaction network reveals new biology and drug candidates: focus on the spike surface glycoprotein and RNA polymerase
Published in Expert Opinion on Drug Discovery, 2021
Esen Sokullu, Maxime Pinard, Marie-Soleil Gauthier, Benoit Coulombe
Upon host cell infection by SARS-CoV-2, replication and transcription of the viral genome made of a single-stranded RNA (ssRNA) molecule is carried out by a multiprotein complex composed of non-structural viral proteins (NSP) (Figure 4). This replication and transcription complex (RTC) is composed of eight NSPs: NSP7-10, NSP12-14 and NSP16; all of which being required for efficient in vivo viral propagation as shown for other nidoviruses [71–74]. These SARS-CoV-2 NSPs are highly similar to their SARS-CoV equivalents (93.29% to 100% homology) [75] and are expressed from the cleavage of two polyproteins translated by the host ribosomes from the 5ʹ portion of the viral genome [76]. Their maturation is carried out by the two viral proteases NSP3 (papain-like proteinase) and NSP5 (3-chymotrypsin-like proteinase) [77,78] that are also promising target for drug development and existing marine natural compounds [79]. Moreover SARS-CoV-2 NSP3 macrodomain was shown to have a stronger interaction with ADP-ribose by docking experiment suggesting also a role in the host antiviral response [8]. Other non-structural proteins are also important in the replication of the viral genome. The nucleocapsid (N) was also shown to be required in viral RNA synthesis of betacoronavirus [80] and SARS-CoV-2 N protein interaction with RNA has been assessed [81].