SARS-CoV-2: Structure, Biology, and Structure-Based Therapeutics Development

Wang, Mei-Yue; Zhao, Rong; Gao, Lijuan; Gao, Xuefei; Wang, Deping; Cao, Ji‐Min

doi:10.3389/fcimb.2020.587269

Cited by 681 publications

(799 citation statements)

References 129 publications

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“…Even in our resource-sharing-rich community, the level and swiftness of data sharing over the last year have been unprecedented. There have been several reviews of SARS-CoV-2 protein structures that have been solved and the insights that the structural details provide into viral mechanisms (Bá rcena et al, 2021;Mariano et al, 2020;Wang et al, 2020). While the number of structures of SARS-CoV-2 biomolecules deposited in the PDB increases weekly, the trends that we report here have remained consistent since we began tracking these details in early 2021.…”

Section: Structural Methodssupporting

confidence: 76%

Structural biology in the time of COVID-19: perspectives on methods and milestones

Lynch

Snell

Bowman

2021

Int Union Crystallogr J

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The global COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has wreaked unprecedented havoc on global society, in terms of a huge loss of life and burden of morbidity, economic upheaval and social disruption. Yet the sheer magnitude and uniqueness of this event has also spawned a massive mobilization of effort in the scientific community to investigate the virus, to develop therapeutics and vaccines, and to understand the public health impacts. Structural biology has been at the center of these efforts, and so it is advantageous to take an opportunity to reflect on the status of structural science vis-à-vis its role in the fight against COVID-19, to register the unprecedented response and to contemplate the role of structural biology in addressing future outbreak threats. As the one-year anniversary of the World Health Organization declaration that COVID-19 is a pandemic has just passed, over 1000 structures of SARS-CoV-2 biomolecules have been deposited in the Worldwide Protein Data Bank (PDB). It is rare to obtain a snapshot of such intense effort in the structural biology arena and is of special interest as the 50th anniversary of the PDB is celebrated in 2021. It is additionally timely as it overlaps with a period that has been termed the `resolution revolution' in cryoelectron microscopy (CryoEM). CryoEM has recently become capable of producing biomolecular structures at similar resolutions to those traditionally associated with macromolecular X-ray crystallography. Examining SARS-CoV-2 protein structures that have been deposited in the PDB since the virus was first identified allows a unique window into the power of structural biology and a snapshot of the advantages of the different techniques available, as well as insight into the complementarity of the structural methods.

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Section: Structural Methodssupporting

confidence: 76%

Structural biology in the time of COVID-19: perspectives on methods and milestones

Lynch

Snell

Bowman

2021

Int Union Crystallogr J

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“…Thanks to the combined world-wide scientific effort and the analysis of SARS-CoV-2 virus (O’Leary and Ovsepian, 2020), successful and safe vaccines are now begin to emerge (Polack et al, 2020;Voysey et al, 2020). Although multiple molecules are at various stages of preclinical and clinical development, there largely remains an unmet need for prophylactic and therapeutic regimens to combat the disease, with proposed measures being scarce and non-specific (Bolarin et al, 2020;Wang et al, 2020a), with the exception of monoclonal antibodies (Baum et al, 2020;Hansen et al, 2020;Weinreich et al, 2020) and dexamethasone (Cain and Cidlowski, 2020;Recovery Collaborative Group et al, 2020), which primarily target hospitalized patients in intensive care units. In this respect, the need for non-expensive therapeutic regimens, safe and effective in non-critically-ill patients and efficient for their management in ambulatory settings, remain unmet.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…An international effort is actually directed towards an efficient therapy (Baum et al, 2020;Hansen et al, 2020;Weinreich et al, 2020), or the development of efficient vaccines (Polack et al, 2020;Voysey et al, 2020). A number of established pharmaceutical molecules and patients’ plasma have been tested as drug candidates for the treatment of COVID-19, with variable results (see (Bolarin et al, 2020;Wang et al, 2020a;Wang et al, 2020b) and references herein). Among the multitude of products tested against COVID-19 disease, a number of natural products, including herbal extracts, have also been assayed (critically reviewed in (Benarba and Pandiella, 2020) and references herein), targeting mainly the viral proteases.…”

Section: Introductionmentioning

confidence: 99%

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A mixture of essential oils from three Cretan Aromatic Plants (thyme, Greek sage and Cretan dittany, CAPeo) inhibits SASR-CoV-2 proliferation:in vitroevidence and a Proof-of-Concept intervention study in mild ambulatory COVID-19-positive patients

Lionis

Karakasiliotis

Petelos

et al. 2021

Preprint

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The need for therapeutic regimens for the non-critically ill patients of the COVID-19 pandemic remains unmet. In this line, repurposing existing drugs, against known or predicted SARS-CoV-2 protein actions, has been advanced, while natural products have also been tested. Previous work has shown that a Cretan Aromatic Plant (Thymbra capitata (L.) Cav., Salvia fruticosa Mill. and Origanum dictamnus L.) essential oil mixture (CAPeo) has a remarkable in vitro antiviral activity against Influenza A & B and Rhinovirus 14 strains, decreasing the symptoms of upper respiratory tract infections, while proven safe in experimental animals and humans. Here, we tested CAPeo in VERO cells infected with SASR-CoV-2. We report that this mixture, at similar concentrations as those previously reported, exhibits a remarkable antiviral activity. Administration of 1 ml of a 1.5% CAPeo in olive oil, in a Proof-of-Concept intervention study in SARS-CoV-2-positive, exhibiting mild COVID-19 symptoms, humans resulted in a significant amelioration of general and local symptoms of the disease. We conclude that CAPeo may be a valuable addition for the prevention and/or treatment of mild COVID-19 ambulatory patients, pending a confirmation through a prospective randomized controlled trial in humans (NCT04705753).

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“…The M protein is the basic type component of the surface of the virus, which delineates inflammatory responses and generates ribonucleoproteins. Although N protein facilitates its entrance and survival inside the host cells, the E protein increases its pathogenicity and acts as an ion channel (Huang et al 2020 ; Sarkar and Saha 2020 ; Wang et al 2020 ). SARS-CoV-2 adapts to a variety of hosts due to high mutation rates (Sarkar and Saha 2020 ; Huang et al 2020 ) (13).…”

Section: Introductionmentioning

confidence: 99%