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BEIJING, May 18, 2020 /PRNewswire=KYODO JBN/ --

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