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Shpichka, et al.
1 Introduction of a highly responsive immune-competent
organism-like platform which is tailored for
Severe acute respiratory syndrome-related SARS-CoV-2 infection and enable real-time and
coronavirus 2 (SARS-CoV-2) that causes high-throughput screening.
coronavirus disease 2019 (COVID-19) has become
a great challenge for not only separate populations 2 Modeling viral infections
but also the whole mankind . This new pathogen
[1]
has almost conquered the world due to the lack 2.1 Humans
of knowledge of COVID-19 pathogenesis and the Nowadays, humans are not a typical object to
absence of any vaccines or approved therapy .
[2]
The use of models enables the possibility to model viral infections that is mainly caused by
learn more about SARS-CoV-2 and infection- ethical issues. However, there is a pool of studies
describing controlled human infection (CHI)
related conditions and to screen drugs and vaccines
efficiently. Unfortunately, the number of approved trials on influenza viruses, respiratory syncytial
models is limited, and researchers have to mainly virus (RSV), etc. For instance, the CHI model
rely on the past experience related to other viruses was used to assess susceptibility and resistance
[9]
(SARS-CoV, Middle East respiratory syndrome to Norwalk virus infection . DeVincenzo et al.
coronavirus [MERS-CoV], influenza A virus experimentally infected adult volunteers with
[IAV], etc.) to develop new relevant models. wild-type RSV (it usually infects children) and
Models based on susceptible animals (ferrets [3,4] , showed that viral load can significantly influence
rhesus and cynomolgus macaques [5,6] , transgenic the disease manifestation and its variation
mice , etc.) are highly demanded in investigations permit achieving the manifestation similar to
[7]
[10]
to study SARS-CoV-2 pathogenesis as well as natural infection . Such controllable adult RSV
clinical signs, and test drugs and vaccines as a part infection model was claimed to be useful for
of the trials. However, high costs, virus species proof-of-concept trials of antivirals candidates.
specificity, and ethical issues do not allow their Human challenge model provided valuable data
use as a routine model. Hence, cell-based models on immune response to influenza infection [11-14] .
[14]
can be a good option for screening and precise Particularly, Huang et al. revealed that antibody-
analysis of molecular pathways of COVID-19 secreting cells are virus-specific and can be the
pathogenesis. However, 2D cultures cannot provide earliest marker of new influenza infection. In the
biomimetic environment that can significantly case of especially dangerous infections (Ebola
influence virus spreading, infectivity, and drug virus, Zika virus, yellow fever virus, etc.), CHI
efficiency. Therefore, 3D tissue models are of trials are significantly limited and almost cannot
particular interest. To date, there is only one 3D be performed. The significant efforts have been
model which is presented by organoids and used for carried out to develop a dengue human infection
studying SARS-CoV-2 infection . Due to the past model which has minimum harm and represents
[8]
[15]
experience, its combination with 3D bioprinting wild-type infection . Hence, if such infection
and microfluidics, and fabrication of a multi-tissue occurs naturally, blood, mucosa, urine, stool, tissue
integrated platform can help create a responsive and biopsies, etc., can serve as appropriate materials
efficient immune-competent organism-like system for studying lifecycle, entry, and pathogenesis of
tailored for SARS-CoV-2 infection (Figure 1). virus, and drug efficacy.
Thus, this review aims to describe the Usually, humans are involved in clinical trials
background of previously used models for viral of actively developed vaccines and phage-based
studies and an approach to design an “ideal” tissue drugs. Particularly, a novel dengue vaccine was
model to study SARS-CoV-2 infection. tested using the DEN2Δ30 model . Moreover,
[16]
The main advantages of each technique and CHI models have enabled the development of the
thus, their combination can allow the fabrication first vaccines against the influenza virus and the
[17]
International Journal of Bioprinting (2020)–Volume 6, Issue 4 11