ConclusionsS-OIV infection can cause severe illness, the acute respiratory distress syndrome, and death in previously healthy persons who are young to middle-aged. None of the secondary infections among health care workers were severe.

Pathogenic RNA viruses are potentially the most important group involved in zoonotic disease transmission, and they represent a challenge for global disease control. Their biological diversity and rapid adaptive rates have proved to be difficult to overcome and to anticipate by modern medical technology. Also, the anthropogenic change of natural ecosystems and the continuous population growth are driving increased rates of interspecies contacts and the interchange of pathogens that can develop into global pandemics. The combination of molecular, epidemiological, and ecological knowledge of RNA viruses is therefore essential towards the proper control of these emergent pathogens. This review outlines, throughout different levels of complexity, the problems posed by RNA viral diseases, covering some of the molecular mechanisms allowing them to adapt to new host species-and to novel pharmaceutical developments-up to the known ecological processes involved in zoonotic transmission.

Surveillance activities for the detection of nosocomial infections at the University of Virginia Hospital (Charlottesville, Virginia) and at hospitals participating in the Virginia Statewide Infection Control Program have focused on outbreaks and device-related infections which are potentially preventable. Eleven outbreaks of nosocomial infections were identified at the University of Virginia Hospital between January 1, 1978 and December 31, 1982 (9.8 outbreaks/100,000 admissions). Ten of the 11 were centered in critical care units. The 269 patients involved in the epidemics represented 0.2% of all hospital admissions and 3.7% of all patients who developed nosocomial infections. Eight of the 11 outbreaks involved infection of the bloodstream, and the 90 patients who developed a bloodstream infection as part of an epidemic represented 8% of all patients with nosocomial bloodstream infections identified during the five-year study period. The reservoir of the 11 outbreaks involved devices (5), contaminated cocaine (1), probable blood products (1), other patients (3), and nursing personnel (1). Forty-one percent of all nosocomial bloodstream infections and 41% of all nosocomial pneumonias occurred in intensive care units (ICUs).In 38 hospitals in the state of Virginia with ICUs and practitioners who voluntarily reported surveillance data between June 1,1980 and May 31,1982, there were 264,757 patients admitted and a crude infection rate of 3%. Of note is that 1,867 of the 7,407 nosocomial infections (25%) occurred in the ICU patients. Several factors point to a compelling argument that the highest priority in infection control resources be assigned to the prevention and control of ICU infections: ICU patients often have serious device-related infections and may be identified as high risk prior to infection. Furthermore, they are at risk of being infected as part of a major outbreak. Such characteristics define a population of hospitalized patients, many of whose infections are preventable.

The crystal structures of monomeric RNA-dependent RNA polymerases and reverse transcriptases of more than 20 different viruses are available in the Protein Data Bank. They all share the characteristic right-hand shape of DNA- and RNA polymerases formed by the fingers, palm and thumb subdomains, and, in many cases, “fingertips” that extend from the fingers towards the thumb subdomain, giving the viral enzyme a closed right-hand appearance. Six conserved structural motifs that contain key residues for the proper functioning of the enzyme have been identified in all these RNA-dependent polymerases. These enzymes share a two divalent metal-ion mechanism of polymerization in which two conserved aspartate residues coordinate the interactions with the metal ions to catalyze the nucleotidyl transfer reaction. The recent availability of crystal structures of polymerases of the Orthomyxoviridae and Bunyaviridae families allowed us to make pairwise comparisons of the tertiary structures of polymerases belonging to the four main RNA viral groups, which has led to a phylogenetic tree in which single-stranded negative RNA viral polymerases have been included for the first time. This has also allowed us to use a homology-based structural prediction approach to develop a general three-dimensional model of the Ebola virus RNA-dependent RNA polymerase. Our model includes several of the conserved structural motifs and residues described in other viral RNA-dependent RNA polymerases that define the catalytic and highly conserved palm subdomain, as well as portions of the fingers and thumb subdomains. The results presented here help to understand the current use and apparent success of antivirals, i.e. Brincidofovir, Lamivudine and Favipiravir, originally aimed at other types of polymerases, to counteract the Ebola virus infection.

As of today, there is no antiviral for the treatment of the SARS-CoV-2 infection, and the development of a vaccine might take several months or even years. the structural superposition of the hepatitis c virus polymerase bound to sofosbuvir, a nucleoside analog antiviral approved for hepatitis c virus infections, with the SARS-coV polymerase shows that the residues that bind to the drug are present in the latter. Moreover, a multiple alignment of several SARS-CoV-2, SARS and MERS-related coronaviruses polymerases shows that these residues are conserved in all these viruses, opening the possibility to use sofosbuvir against these highly infectious pathogens.

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