Ομιλία – Παρουσίαση: Αχιλλέας Γραβάνης, Καθηγητής Φαρμακολογίας, Ιατρική Σχολή Πανεπιστήμιο Κρήτης, Ερευνητής, Ινστιτούτο Μοριακής Βιολογίας & Βιοτεχνολογίας του ΙΤΕ

1. COVID-19 PHARMACOLOGY
Achilleas Gravanis
Professor of Pharmacology, Medical School University of Crete
Affiliated Research Professor, Center Drug Discovery Northeastern University

2. ΕΜΒΟΛΙΑΕΜΒΟΛΙΑ
REMDESIVIR
THERAPY
(about 1200 clinical trials)
ΕΜΒΟΛΙΑ
ANTIBODIES
AGAINST VIRAL
PROTEINS
ANTIVIRALS
IMMUNE
MODULATORS
PROTECTION
(about 140 vaccines )
VACCINES
DNA
RNA
VIRAL
ANTIGENS-
PARTICLES
FAVIPIRAVIR
NEW
CHLOROQUINE
ANTIBODIES
IL6-R, Ca5
PLASMA
SYNTHETICANTIBODIES
AGAINST
VIRAL
RECEPTORS
ACE2,CCR5

3. REMDESIVIR
THERAPY
ANTIVIRALS
FAVIPIRAVIR
NEW
ANTIBODIES
AGAINST
VIRAL
RECEPTORS
ACE2,CCR5
No effective antivirals exist so far. We need more research and clinical
evaluation for effective SARS-CoV-2 antiviral small molecules. Today,
i.v. Remdesivir helps severely ill patients with Covid19. Its future
derivatives or metabolites may be proved effective in early patients, if
given p.o., i.m or by inhalation.
Recently available crystallography data for the structure of SARS-
CoV-2 polymerase and protease, in silico molecular dynamics and AI
algorithms will facilitate to advance repurposing of existing drugs and
design selective corona virus inhibitors.
Testing of existing polymerase-protease inhibitors specific for other
viruses (EBOLA, SARS, MERS, HIV, Influenza) is ongoing.
Efforts are also targeting the cellular receptors of SARS-CoV-2, ACE2,
NPL1 proteins, to block infection of receptor expressing cells.

4. THERAPY
ANTIBODIES
AGAINST VIRAL
PROTEINS
PLASMA
SYNTHETIC
Convalescent plasma from SARS-CoV-2 recovered patients is the
source for the idea of producing antibodies against viral proteins, as
antiviral agents
Isolation, chemical characterization and production of cDNAs for
specific antibodies gave birth to antiviral proteins
SARS-CoV-2 protein S and proteins NSPs are the major selected
antigens.
Animals with humanized immune system are used for immunization
and production of human viral antibodies.
Mixtures of monoclonal antibodies against SARS-Cov-2 viral proteins
may be the first effective antiviral treatment.

5. The genetic sequence of SARS-CoV-2 was published on January 11,
2020.
The collaboration among scientists and biopharmaceuticals has
produced about 140 preclinically confirmed active vaccine candidates.
In addition to the complexity of finding the most effective vaccine
candidates, the massive production process is also very important for
producing the vaccine to the huge scale needed to cover world
population.
Biotechnological technologies based on DNA or mRNA that offer more
flexibility compared to neutralized viral particles or proteins-antigens
will speed the vaccine development. Recombinant protein-based
technologies are easily applied to large-scale production capabilities.
However, these new technologies did not offer yet a successful
vaccine.
Use of an adjuvant is pivotal, allowing more people to be vaccinated
and conserving antigen resources.
ΕΜΒΟΛΙΑΕΜΒΟΛΙΑ
ΕΜΒΟΛΙΑ
PROTECTION
VACCINES
DNA
RNA
VIRAL
ANTIGENS-
PARTICLES

6. THERAPY
IMMUNE
MODULATORS
CHLOROQUINE
ANTIBODIES
IL6-R, Ca5
Different types of immunomodulation were tested, through repurposing
existing drugs, to control hyperinflammation due by cytokine release.
Interleukin (IL) inhibitors, Janus kinase (JNK), (BTK) Kinase inhibitors and
interferons are just a few of the drugs that are in clinical trials.
Antimalarial Chloroquine was among the first ones with limited efficacy, based
on controversial clinical data, and important cardiotoxicity which questions its
usefulness.
Neutralizing monoclonal antibodies against pro-inflammatory Interleukin-6
receptors and complement Ca5 protein were among the most promising, to
control cytokine storm and lung destruction.

7. CONCLUSIONS
We need more research and clinical evaluation for effective SARS-CoV-2 antiviral small
molecules. Today, i.v. Remdesivir helps severely ill patients with Covid19, new
derivatives or metabolites may be proved more effective in early patients, given p.o.,
i.m, or by inhalation.
First SARS-CoV-2 antivirals might be the antibodies against viral proteins. Multiple
advanced clinical trials may offer them by the end of 2020.
The genome of SARS-CoV-2 virus is rather stable (at least as stable as influenza virus).
SARS-CoV-2 infected patients develop antibodies, we still don’t know for how long.
Effective, non-toxic vaccines may come next summer. New technologies (DNA, RNA
vaccines) may accelerate their massive production.
Symptomatic therapies, controlling the effects of SARS-CoV-2 on inflammation-
cytokine storm, blood coagulation-thrombosis, heart function help today many
severely ill Covid19 patients. Their combination with antivirals, depending upon the
stage of the disease and type of patients may further ameliorate treatments.

8. Pressure for therapies and prophylaxis of SARS-CoV-2
pandemic must not jeopardize safety and true efficacy
of future drugs and vaccines.
Thus,
Well designed, randomized controlled, clinical trials
are needed to avoid problems!