Day 1 :
University of North Carolina at Chapel Hill, USA
Keynote: The small molecule nucleoside prodrug GS-5734 exhibits broad antiviral activity against pathogenic human coronaviruses and related zoonotic strains
Time : 09:30-09:55
Amy Sims completed her PhD in Microbiology and Immunology from Vanderbilt University in 2001 and performed postdoctoral studies at the University of North Carolina at Chapel Hill with Dr. Ralph Baric. She is currently a Research Assistant Professor at UNC Chapel Hill. Her work has focused on understanding highly pathogenic human coroanvirus replication in primary human cell types as well as identifying novel drugs and therapeutics that are effective against epidemic coronavirus strains.
SARS and MERS coronaviruses (CoVs) emerged from zoonotic reservoirs, causing global disease with high mortality rates. Reemergence is likely, as viruses very similar to SARS- and MERS-CoV are circulating in bat populations. Currently, there are no effective vaccines or therapeutics available to prevent or treat SARS-CoV, MERS-CoV or related zoonotic strain infections. GS-5734, a prodrug of an adenine C-nucleoside analog with known activity against filoviruses, is currently undergoing clinical testing for the treatment of Ebola virus infection. We assessed the activity of GS-5734 against SARS-CoV- and MERS-CoV-infected human airway epithelial cell (HAE) cultures, a physiologically relevant in vitro human conducting airway model. HAE cultures were infected with either SARS-CoV or MERS-CoV expressing fluorescent reporter genes at a multiplicity of infection of 0.5. Concurrent with infection, cultures were incubated in media containing serially diluted compounds for the duration of the study (48 hours). Levels of infection were assessed using immunofluorescence, viral titration and real-time PCR analysis of replication-specific viral RNA species. GS-5734 was found to have potent activity against SARS-CoV and MERS-CoV, with 90% inhibition at less than or equal to 150 nM. In addition, GS-5734 significantly reduced the replication of multiple alpha- and beta-coronaviruses (groups 2b and 2c) in HAE cultures, including zoonotic ancestors of epidemic coronaviruses. Importantly, GS-5734 has shown low in vitro cytotoxity, with 50% cytotoxic concentrations > 1 µM in multiple human cell types. These data demonstrate the broad antiviral activity of GS-5734 against human epidemic and novel bat CoV strains that have future pandemic potential.
President Foundation T. & L. de Beaumont Bonelli for cancer research, Italy
Time : 09:55-10:20
Giulio Tarro graduated from Medicine School, Naples University (1962). Research Associate, Division of Virology and Cancer Research, Children’s Hospital (1965-1968), Assistant Professor of Research Pediatrics, College Medicine (1968-1969), Cincinnati University, Ohio. Oncological Virology Professor, Naples University (1972-1985). Chief Division Virology (1973-2003), Head Department Diagnostic Laboratories, (2003-2006). D. Cotugno Hospital for Infectious Diseases, Naples; Emeritus, 2006 -. Since 2007 Chairman Committee of Biotechnologies and VirusSphere, World Academy Biomedical Technologies, UNESCO, Adjunct Professor Department Biology, Temple University, College of Science and Technology, Philadelphia, recipient of the Sbarro Health Research Organization lifetime achievement award (2010). President Foundation de Beaumont Bonelli for Cancer Research.
The Variola major, the virus thatcauses the smallpox, lethal virus in the 30% of the cases, waseraticated in 1979 in the human species, thanks to a capillaryvaccination on global scale.rnRecently the Word Health Organization (WHO) declaredthat India and Southeast Asia are polio-free, really a greatachivementsince the vaccine for polio, an infectiousdeseasethat can cause paralisis, wascertificatedsafe and usefulonly 60 years ago.rnLast year over 800 milliondoses of combinationvaccines are going to be used to vaccinate Chinesechildrenwhereas more than 20 millionchildrenworldwide do notreceiveone or more importantvaccinationsthatwouldprotectthem from atleastonepreventabledisease.rnHBV virus, responsible for epatitis B infection, isable to prevent 50% of alllivercancers. Human Papilloma Viruses (HPV) havebeencorrelated with the cervicalcancer (genotypes 16 and 18 particularlyoncogenic in humans): the USA Food and Drug Administration (FDA) in 2006 released the first vaccine against HPV.rnLong years of researchwhererequired for busting the new system to fightcancer. Researchisgoing to obtain the complete sequence by proteomicsapproaches, in order to achieveadequateantigenpreparationsthatmight be used to generate assays for a specificanticancer vaccine.rnFinally, the ability of the immune system to recognize a tumor-associatedantigen, thusenablingdevelopment of a vaccine approach for therapeuticapplication, represents a main target of thisfield of researchrn
San Raffaele Scientific Institute Milan, Italy
Time : 10:20-10:45
Daniela Maria Cirillo is a board certified clinical microbiologist, Head of the Emerging Bacterial Pathogens Unit at the San Raffaele Scientific Institute (HSR) in Milan, Italy and Director of the WHO SRL, Collaborating Center ITA98, Italian Reference Centre for Mycobacterial Typing. The main fields of interest are: research on new diagnostic for MDR/XDR-TB, M.tuberculosis pathogenesis, virulence markers, host pathogens interaction, NTMs and nosocomial pathogens. rnAuthor of more than 130 peer-reviewed original papers.rnInternational appointments: Elected member of the ECDC TB disease Coordinating Committee, CoChair of the New Diagnostic Working Group of the Stop TB partnership, Core Group elected member of the Global Drug Resistance Initiative (GDI) of the Stop TB partnership-WHO, member of Global Laboratory Initiative, member of the Core Group of the ERLN-TB. On-going international grants: CRYPTIC 1 (2015-17) and 2 (2016-19) consortium coordinated by Oxford University, ReSeq TB supported by the BMGF, E-Detect TB EU-Health (2016-19)rnShe is currently involved in the WGS Global Surveillance Molecular project coordinated by WHO.rn
The rapid progresses in M.tuberculosis (MTB) whole genome sequencing (WGS) allow to collect diagnostic information including prompt and accurate identification and prediction of resistance to all anti-mycobacterial drugs, with an high gain in term of time to results and cost-containment.rnCurrent diagnosis of tuberculosis (TB) is based on culture and commercial molecular based assays. Data obtained by phenotypic sensitivity tests are available with large and do not provide a rapid feedback on response to therapy thus impairing the possibility to implement an appropriate individualized treatment. In addition, for long time MTB has been considered a single pathogen, and the association between lineages and drug resistance (DR) was largely underestimated. The major challenge to use SNPs detection for clinical management is the clear understanding of their correlation to the clinical outcome. In order to achieve this goal, a global public-private partnership has been established to develop a Relational Sequencing TB Data Platform (ReSeqTB) to simplify and standardize whole genome sequencing data analysis for interpretation of antimicrobial drug resistance. Based on an exhausting literature review and WGS performed at reference centers worldwide, we have scored the likelihood ratios of each mutation to be associated to drug resistance. A list of 44 mutations to 10 drugs with moderate to high confidence associations with DR phenotypes was identified. Using the PhyResSE web tool (www.phyresse.org) we analyze WGS of early positive liquid cultures and report complete genotypic data (that can overrule phenotypic findings) within 5 working days. rn
Associate Director Medical Scientific Liaison Europe,Abbott Diagnostics, Italy
Time : 10:45-11:10
Claudio Galli graduated in Medicine at the “Sapienza” University in Roma (Italy) in 1980, then specialized in Gastrointestinal Diseases and completed his PhD in Infectious Diseases at the same institution. He is the Associate Medical Director for Europe at Abbott Diagnostics, one of the largest companies in this sector. He has published 62 papers on indexed journals, with a major focus on viral hepatitis and HIV infection, and is a reviewer for several high impact medical journals. He is an active member of several Italian and international scientific societies and since 2005 he is recognized in Who’s who of professionals.
Several direct antiviral agents (DAAs) for the treatment of chronic hepatitis due to the hepatitis C virus (HCV) have been recently approved. Since these drugs allow to achieve a sustained response rate >95%, there is an enhanced need for the implementation of screening strategies aimed to the identification of “silent” HCV carriers in order to obtain a clearer picture on the real burden of infection and to plan for therapeutic interventions. While more than 65% of cases of chronic hepatitis, cirrhosis and hepatocellular carcinoma are linked to a chronic HCV infection, the modes of acquisition over time and the routes of infection show profound differences. Incidence data, when available, show a decrease over the last decades; prevalence data are not reliable since most studies have been carried out several years ago and in small population samples. Surveillance systems are mostly based on the reporting of symptomatic cases and rely on the detection of anti-HCV antibodies alone or on the combination of anti-HCV and HCV-RNA. Since the rate of active infections among anti-HCV positive, asymptomatic subjects ranges from 60% to 80% and usually decreases with age, the former strategy will overestimate the number of HCV-infected individuals and also underestimate the total number of subjects who encountered HCV, because a spontaneous clearance of HCV followed by the negativization of anti-HCV has been reported. Several screening algorithms that include HCVAg testing have been proposed; the sensitivity of current assays corresponds to about 1,000 UI/mL of HCV-RNA, a level usually attained in untreated subjects