Boletín que incluye información científica sobre el COVID-19, incluye artículos científicos y artículos preprint actualizados al 03 de Julio de 2020.

Boletín que incluye información científica sobre el COVID-19, incluye artículos científicos y artículos preprint actualizados al 18 de Junio de 2020.

Boletín que incluye información científica sobre el COVID-19, incluye artículos científicos y artículos preprint actualizados al 19 de Junio de 2020.

COVID-19 is rarely reported in children and they are mildly affected in most cases. The most common clinical presentation of COVID-19 is cough, fever and sore throat; severe cases show tachypnea. The course of the disease is from one to two weeks. Laboratory findings are nonspecific; lymphopenia, elevation of C-reactive protein and procalcitonin have been described. Early chest X-ray is usually normal, and the most common tomographic findings are consolidations with halo, ground-glass opacities and tiny nodules which mainly affects subpleural areas. Management of the disease is supportive; in severe cases, it should be focused on respiratory support. It is recommended to limit the handling of respiratory secretions and to follow the same preventive measures provided to adults. / Revisión por pares

Thesis (M. Med. Sc.)--University of Hong Kong, 2009. / Includes bibliographical references (p. 61-67).

Thesis (Ph. D.)--University of Texas at Austin, 2002. / Vita. Includes bibliographical references. Available also from UMI Company.

Not available / text

Thesis (M. Med. Sc.)--University of Hong Kong, 2007.

Thesis (Ph. D.)--University of Texas at Austin, 1998. / Vita. Includes bibliographical references (leaves 97-111). Available also in a digital version from Dissertation Abstracts.

SARS-CoV-2, the coronavirus responsible for the CoVID-19 syndrome, continues to be a major public health crisis worldwide. While the ongoing vaccination development and deployment efforts are a critical first line of defense, small-molecule therapeutics are needed to treat those who are infected and in desperate need of medical attention. Perhaps the most studied coronaviral target is the 3CL protease enzyme responsible for the proteolytic processing of the viral polyproteins pp1a and pp1ab which is essential for viral replication. We evaluated a series of five new compounds with four containing an (acyloxy)-methyl ketone reactive group including clinical candidate Pf-00835231 for their inhibitor potencies against SARS-CoV23CL protease. All five compounds exhibit remarkable potencies with Kivalues in the high picomolar to low nanomolar range against SARS-CoV-2. The X-ray structures of all five compounds were determined in complexes with SARS-CoV-2 3CLpro to between 1.4 Å and 1.6 Å resolution. All five compounds are observed to form a covalent bond with catalytic Cysteine 145 with four compounds forming adducts with the expected tetrahedral geometry. Compound 4 however, which contains an (acyloxy)-methyl ketone warhead, was found to form an adduct with bond geometries similar to an episulfonium cation. Despite possessing similar chemistry and scaffolds, inhibitor binding to the SARS-CoV-2 3CLpro induced a variety of subtle active site conformational differences, particularly in the S2/S4 separating strand and connecting strands.<div><br></div><div>Understanding substrate specificity in coronaviral main protease is essential for designing competitive inhibitors. While first principles are already established, including a Q/X cleavage-site (where X is either Alanine or Serine), differences exist between α, β, γand δ clades that are important for recognition, and ultimately inhibitor design. Covalent complexes of SARS-CoV-2 and avian infectious bronchitis virus (IBV) covalently bound, in trans, to the C-terminus of the same enzyme have been crystallized and modeled at 2.6 and 2.2 Å, respectively. The similarities and differences in their binding are described in chapter 6.<br></div><div><br></div><div>Middle-East Respiratory Syndrome Coronavirus is a re-emergent zoonotic pathogen with a 30% mortality rate in humans. The positive-sense single-stranded RNA genome is translated by the into polyproteins 1a (pp1a) and polyprotein 1ab (pp1ab). Pp1ab contains the constituents of the viral RNA-dependent RNA polymerase complex. These must be cleaved by 3CLpro, which is contained within this pair of polyproteins, before viral replication and transcription may occur. Attempts to drug this cysteine protease have proven difficult since competitive inhibitors activate the Wild-Type protease at low concentrations via a non-competitive binding mechanism. This mechanism is mediated by non-conserved residues in regions that are distal to the catalytic site. During the viral life-cycle these residues modulate recognition This study focuses on determining the identities of these residues and their effects on the dose-response curves of established competitive inhibitors of Coronaviral 3CLpro. It also explores how the residues in these regions synergize to effect intrinsic kinetic parameters of this family of enzymes including turnover (kcat) and dimer dissociation constant (KD). Additionally, a rapid-equilibrium kinetic model was developed to rationalize this unique phenomenon where competitive inhibitors cause significant activation of the enzyme’s activity.<br></div>