Since the outbreak of COVID-19, researchers at the Wuhan Institute of Virology 
(WIV) of the Chinese Academy of Science (CAS) have been working on the 
frontline, undertaking a range of R&D tasks to prevent and control the 
pandemic. Still, rumors swirling around the internet have spread around the 
world claiming that the novel coronavirus was synthesized and that the pandemic 
was caused by a leak from the lab.

In order to present a comprehensive overview of the work into pandemic 
prevention and control being done by researchers at the WIV, and to share their 
frontline experiences with the world, Science and Technology Daily conducted an 
exclusive interview with Yuan Zhiming, president of the CAS Wuhan Branch and 
director of Wuhan National Biosafety Laboratory, and Guan Wuxiang, deputy 
director general of the WIV.

Working all out since Dec. 30, 2019

Science and Technology Daily: When did the WIV begin its research and 
development work into COVID-19? What was the first task you received?

Guan Wuxiang: The WIV's efforts in this regard began on Dec. 30, 2019. Upon 
receiving samples of an "unknown pneumonia" from Wuhan Jinyintan Hospital, we 
organized our top experts in the field to conduct pathogen detection and 
identification overnight, and promptly reported their findings to the relevant 
authorities.

Science and Technology Daily: What R&D tasks have the WIV undertaken concerning 
the prevention and control of the pandemic since the start of the COVID-19 
outbreak? How have these tasks progressed?

Guan Wuxiang: Since the outbreak began, the WIV has carried out various R&D 
works in an orderly manner. These include isolating and identifying the virus, 
detecting pathogens, developing antiviral drugs and vaccines, evaluating the 
titer levels of neutralizing antibodies in recovering patients' plasma, 
establishing animal-based models, and researching pathogenic mechanisms. The 
progress made in these areas has provided scientific and technological support 
for frontline pandemic prevention and control.

The WIV has achieved a series of breakthroughs in terms of virus isolation and 
identification. It has sequenced the whole genome of the virus, isolated the 
virus strain, identified it as a novel coronavirus, and completed standardized 
virus cryopreservation. On Jan. 11, as one of the designated institutes of the 
National Health Commission, the WIV submitted the virus' sequence to the World 
Health Organization.

In terms of detecting COVID-19, the WIV has quickly organized its R&D efforts 
to develop nucleic acid tests and serological detection technologies. COVID-19 
nucleic acid testing kits, jointly developed by the WIV and Uni-medica, are 
currently under emergency approval by the National Medical Products 
Administration (NMPA). The WIV has also worked with Zhuhai Livzon Diagnostics 
to develop a COVID-19 serological test kit, which was approved by the NMPA on 
March 14 and certified for medical use. As a designated institute by Wuhan 
city, the WIV has participated in the task of detecting the COVID-19 pathogen. 
Over 6,500 throat swab samples of suspected COVID-19 cases have been tested by 
the WIV since Jan. 26.

The WIV has also worked with the National Engineering Research Center for Drugs 
of Emergency Prevention and Control of the Institute of Military Medicine under 
the Academy of Military Sciences to select and evaluate marketed drugs, 
clinical drugs and drug candidates. We found that chloroquine phosphate and 
favipiravir have shown fairly positive antiviral effects against the novel 
coronavirus at the cellular level. Other drugs have also been selected and are 
currently being evaluated. In the meantime, the WIV has been working with the 
China National Biotec Group (CNBG) of the China National Pharmaceutical Group 
(Sinopharm) to research and develop an inactivated whole virus vaccine. This 
vaccine was approved by the NMPA for clinical trials on April 12.

In addition, the WIV and the CNBG have also evaluated the titer levels of 
neutralizing antibodies in the plasma of recovering patients. We found that the 
antibody titers reached 1:640. After further evaluation, the organizations 
involved carried out clinical trials according to the relevant procedures.

As for establishing animal models, the WIV has completed COVID-19 modelling in 
rhesus monkeys. Evaluated by experts organized by the Ministry of Science and 
Technology, the model is considered to have been successful, and can be used to 
conduct research into the pathogenic mechanisms and spread of COVID-19. This 
provides a significant platform for evaluating vaccines and drugs for the novel 
coronavirus.

Science and Technology Daily: As an institute that specializes in studying 
viruses, how has your previous experience into virus research helped in the 
fight against the COVID-19 outbreak?

Guan Wuxiang: The WIV began construction of the Wuhan National Biosafety 
Laboratory following the 2003 SARS epidemic. The Institute focuses on virus 
research, especially on highly pathogenic viruses. We have carried out basic 
research into and developed prevention and control technologies for a variety 
of viruses, which laid the foundation for coping with outbreaks of new 
infectious diseases.

In particular, the Institute's research team has been studying coronaviruses 
for over a decade. It is equipped with general nucleic acid testing techniques 
for coronaviruses, commonly used methods for detecting nucleic acid and 
antibodies of SARS-like coronaviruses, and virus isolation and cultivation 
methods. These all played an important role in the identification of pathogens 
during the early stage of the COVID-19 outbreak.

Science and Technology Daily: Considering the Institute's years of experience 
researching coronaviruses, is it possible to predict novel coronavirus 
outbreaks?

Guan Wuxiang: Since the SARS outbreak in 2003, China has improved its 
infectious disease surveillance system and further strengthened its infectious 
disease prevention and control capacity by means of special support projects 
for researching major infectious diseases. The existing system is mainly 
focused on the surveillance of and the early warning for infectious diseases. 
Currently, it is not possible to actively predict outbreaks.

Forecasting virus outbreaks and pandemics is a difficult task all across the 
world. Humans are not fully aware of all the viruses that exist in nature and 
the patterns of their occurrence, development, spread and pathogenesis. To 
develop from the current level of passive warnings to the level of active 
forecasting, a group of diligent researchers are needed to continue basic 
research and technological development. Carrying out long-term monitoring and 
investigation of viruses found in wild animals is an important task in 
monitoring possible infectious diseases. 

Well-organized research and development teams

Science and Technology Daily: At present, how many teams at the WIV are 
carrying out scientific research into COVID-19? What exactly are they doing?

Guan Wuxiang: According to the development of the epidemic and the tasks being 
undertaken, the Institute organized over 120 top researchers from different 
subfields into 12 scientific research teams. They are mainly responsible for 
carrying out pathogenic testing, virus monitoring, drug screening and other 
work. In addition, more than 40 people from six support teams were organized to 
provide assistance for the scientific research work. The national virus 
resource database is responsible for the collection and standardization of 
COVID-19 samples; the biosafety level 3 (BSL-3) laboratory and biosafety level 
4 (BSL-4) laboratory are mainly responsible for the normal operation of the 
laboratories and the guarantee of the scientific researchers' safety. 
Meanwhile, the analysis and testing center and the experimental animal center 
are responsible for the analysis and testing of large instruments and the 
protection of the safety of laboratory animals, respectively.

Science and Technology Daily: What does a typical work day consist of for the 
scientific researchers?

Guan Wuxiang: Since the COVID-19 outbreak began, the researchers at the WIV 
have been fighting on the frontlines against the epidemic. They volunteered to 
forgo the Spring Festival holiday, overcame all kinds of personal difficulties, 
and devoted themselves to researching COVID-19.

The lab's researchers work shifts lasting around five to six hours, during 
which they are unable to eat, drink or use the toilet. Taking into account the 
time spent on preparation and data processing, they work an average of around 
10 to 12 hours a day. In order to efficiently utilize the research machinery, 
multiple teams take turns to enter the BSL-3 labs in the Xiaohongshan and 
Zhengdian Scientific Park to carry out research. The team responsible for 
pathogen detection, which has a large number of samples to work on, is divided 
into two groups that take turns to work in the BSL-3 and BSL-2 labs.

Hearing that our COVID-19 pathogen detection team didn't have enough 
researchers to conduct detection of so many samples, many of the Institute's 
young people volunteered to take part in pathogen testing.

BSL-4 Laboratory's contribution and achievements

Science and Technology Daily: Could you please highlight the major 
breakthroughs and progress made by the BSL-4 Laboratory in terms of scientific 
and research advancement?

Yuan Zhiming: The BSL-4 Laboratory is actually a subsidiary of the Wuhan 
National Biosafety Laboratory. In addition, there are also two BSL-3 Labs, 
numerous BSL-2 Labs affiliated to the WIV, several ordinary labs, as well as 
facilities and supporting equipment for animal testing. The aforementioned labs 
and institutes constitute a cluster platform to safeguard biosafety.

After receiving samples of a then-unidentified pneumonia virus and successfully 
isolating the new coronavirus pathogen, the Wuhan National Biosafety Laboratory 
then applied for a number of accreditations that later enabled it to cultivate 
COVID-19 pathogenic cells and test them on infected rodents and non-primate 
animals. In addition, the lab's scientific research ethics supervisory 
committee and its animal testing management body have guaranteed the welfare of 
all animals used in trials by managing, observing and checking the whole 
process before providing their approval.

Therefore, the Wuhan National Biosafety Laboratory has made overall progress in 
several areas, including, purification of the proliferation of the COVID-19 
virus, assessment into neutralizing antibody titers from the plasma of 
recovered patients, evaluation of the effects of disinfectants, assessment of 
the establishment of non-primate animals' experimental models and antibody 
medicines, development of inactivated vaccines, and trials on animal 
protection. So far, our achievements have encompassed the standardized 
techniques of virus proliferation and inactivation, the rollout of new 
disinfectants, the assessment of COVID-19's inactivation, the modeling of 
infections in rhesus monkeys and evaluations on candidate antiviral medicines 
and inactivated vaccines. The established model for animals has also provided a 
fundamental basis for evaluating other candidate antiviral medicines and 
vaccines.

Stringent protocols taken to avoid virus leaks

Science and Technology Daily: What preventive and protective measures do 
personnel take when both entering and exiting the BSL-4 Laboratory, where 
biological safety controls are among the strictest?

Yuan Zhiming: All those working in the BSL-4 Laboratory must undergo 
theoretical and practical training and pass evaluations for physical and 
psychological competences. Even if they pass those accreditation tests, they 
won't be given access until they receive permission from their directors.

Upon arrival at the entrance to the lab, researchers' basic physical 
conditions, such as blood pressure and body temperature, are checked to ensure 
they are within the appropriate ranges for working inside the lab. Throughout 
the entire process, only researchers endorsed with the requisite qualifications 
and accreditations can unlock the door leading to the lab's ring corridors. It 
is there that they will examine the operations of the lab, complete the 
entrance and exit form, and inform the monitoring center.

Following the first access, researchers will enter the first fitting room after 
unlatching a second door. Here, they change into disposable protective suits 
and check and put on the positive-pressure protective suit, before connecting 
it to a breathing supply hose. After these procedures are complete, they will 
pass through a decontamination shower room before arriving at the main 
laboratory room. In order to guarantee biosafety, there must be no fewer than 
two testing personnel working at the same time in the lab. Access is denied to 
anyone who wishes to enter the lab alone.

Researchers generally exit the laboratory via the same route they enter. Before 
researchers exit, chemical disinfection and water rinsing must be performed in 
the decontamination shower room, and the positive pressure protective suits 
must be thoroughly disinfected. After removing the inner protective suit, all 
personnel must shower and then put on their own clothes, exit the laboratory, 
and fill out the Laboratory Personnel Entry and Exit Registration Form. At this 
point, a lab shift is complete.

Inside the laboratory, all contact between researchers and the outside world is 
made through the monitoring center. In the case of any abnormal situation, the 
researchers will first contact the center as soon as possible. When experiments 
are underway, the monitoring center will also be staffed with biological 
safety, biological security and equipment support personnel throughout to 
ensure that any potential emergency can be properly handled.

Science and Technology Daily: In terms of preventing virus leaks from the 
laboratory, what special protective technologies and measures does the BSL-4 
Laboratory utilize?

Yuan Zhiming: The core of the Wuhan BSL-4 Laboratory is surrounded by 
stainless-steel walls, forming a "box-within-a-box" structure. The core lab 
enclosure can ensure sufficient structural strength and tightness to form a 
static seal. The lab's dynamic seal uses negative pressure technology to ensure 
a strict and orderly pressure gradient between the functional areas, thereby 
effectively preventing any air contaminated by infectious pathogenic 
microorganisms from spreading to areas with low contamination probability and 
to the external environment.

Air emitted from the lab is filtered and discharged by two-stage 
high-efficiency filters to ensure the safety of the emissions. Waste water is 
discharged after high-temperature treatment in a sewage treatment system. 
Polluted waste in the lab is subjected to high-temperature and high-pressure 
treatment by double-door autoclaves, and then safely removed and delivered to a 
centralized medical waste disposal unit with corresponding qualifications for 
disposal. Whenever personnel pass through the entrance and exit channels, their 
positive pressure protective suits are chemically disinfected using the 
chemical showers to ensure the safety of the passageways. The above technical 
protection measures ensure that viruses inside the lab cannot escape.

The laboratory not only has high-standard biological safety facilities, but 
also a strict biological safety management system, including a series of 
procedural documents and standard operation manuals on scientific research 
programs, personnel, laboratory animals, waste disposal and infectious material 
management. These ensure that the lab runs safely and efficiently. The physical 
facilities of the laboratory are tested annually by a third-party organization, 
and its operations are subject to supervision and evaluation by the China 
National Accreditation Service for Conformity Assessment, as well as annual 
inspections by relevant national authorities.

Science and Technology Daily: Research into the COVID-19 virus will take a long 
time. What follow-up work will be done in the future?

Guan Wuxiang: The WIV will continue to face the urgent scientific and 
technological needs for rapid handling and emergency response. It will also 
carry out scientific research and make breakthroughs into the testing of 
pathogens, development of antiviral drugs and vaccines, evaluation of 
neutralizing antibody titers in recovering patients' plasma, and research 
animal models and pathogenic mechanisms. 

Facing the long-term demand for the prevention and control of infectious 
diseases, the Institute will continue to conduct basic research and development 
into prevention and control technologies in the fields of biosecurity and 
public health. It will also provide scientific and technological support and 
decision-making consultation in order to safeguard biosecurity.

SOURCE  Science and Technology Daily