Banca de QUALIFICAÇÃO: LUCAS MATHEUS STANGHERLIN

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : LUCAS MATHEUS STANGHERLIN
DATE: 22/06/2023
TIME: 14:00
LOCAL: Sala 307 do Bloco B do Campus de Santo André da Universidade Federal do ABC
TITLE:

"Evolutionary Study of Betacoronavirus Spike Proteins and Their Receptors."

PAGES: 138
BIG AREA: Ciências Biológicas
AREA: Genética
SUBÁREA: Genética Molecular e de Microorganismos
SUMMARY:

Abstract
Emerging zoonoses are defined as pathologies that can be caused by various etiological
agents, often viruses, which have recently undergone spillover events from animal pop-
ulations to human populations, potentially causing high-scale contagion. Humanity has
recently experienced a three-year pandemic caused by a coronavirus called SARS-CoV-2,
which has affected and claimed the lives of millions of people worldwide. This virus belongs
to the genus Betacoronavirus, which includes other important viruses for human health
that have caused epidemics, such as the SARS-CoV responsible for an epidemic in 2003 and
the MERS-CoV in 2012. It is within this context that this study seeks to investigate the
evolutionary history of Spike proteins (critical for cellular invasion) of betacoronaviruses,
along with their respective receptor proteins, and relate them to the dynamics of receptor-
ligand interactions in order to find answers regarding mutations that lead to spillover
of these viruses into human populations and how selective pressure acts on the involved
proteins. To achieve these objectives, the sequences of Spike proteins from betacoron-
aviruses and their receptor proteins were obtained, processed, and aligned to estimate their
phylogenies. Thus, the probabilities of occurrence of positive codon-by-codon selective
pressure were estimated for the coding regions of these proteins. The nature of interactions
in the receptor-ligand complex was also analyzed and related to evolutionary processes. A
high probability of positive pressure was detected in a large number of residues of Spike
proteins from a wide range of betacoronavirus species and variants, as well as in receptor
proteins from various mammalian orders, with a high concentration of these mutations
in important interaction regions. Finally, it was also determined that the nature of the
interaction between residues of Spike proteins of SARS-CoV-2 and the ACE2 receptor in
the interaction interface changed dramatically between each of the variants. The results
support the Red Queen hypothesis, which states that the coexistence and interaction
between pathogens and hosts are an evolutionary driver for both parties involved, selecting
viruses that harbor mutations in viral proteins that increase the virus’s fitness, ranging
from enhanced invasive capacity to immune system evasion. The same occurs with hosts
that harbor mutations in proteins that provide greater resistance to infection. The results
presented here provide new insights into the evolutionary race between coronaviruses and
their hosts, and further analyses will be conducted to shed more light on the history of
adaptations in Spike proteins during spillover events into human populations.

COMMITTEE MEMBERS:
Presidente - Interno ao Programa - 1676356 - ANTONIO SERGIO KIMUS BRAZ
Membro Titular - Examinador(a) Interno ao Programa - 927.634.300-82 - HELENA BEATRIZ DE CARVALHO RUTHNER BATISTA VICENTE - UFRGS
Membro Titular - Examinador(a) Externo à Instituição - MARCELO BROCCHI - UNICAMP
Membro Suplente - Examinador(a) Externo ao Programa - 1640121 - LUCIANA CAMPOS PAULINO